Herbal Treatments for Depression

Destroy Depression

Destroy Depression is written by James Gordon, a former sufferer of depression from the United Kingdom who was unhappy with the treatment he was being given by medical personnell to fight his illness. Apparently, he stopped All of his medication one day and began to search for answers on how to cure himself of depression in a 100% natural way. He spent every waking hour researching all he could on the subject, making notes and changing things along the way until he had totally cured his depression. Three years later, he put all of his findings into an eBook and the Destroy Depression System was born. The Destroy Depression System is a comprehensive system that will guide you to overcome your depression and to prevent it from injuring you mentally and physically. Read more here...

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See also Tricyclic antidepressants General Information

Overall, amoxapine appears to have some advantage over other tricyclic antidepressants possible earlier onset of action and relative freedom from serious cardiotoxic effects. Its major drawbacks are the potential for neuroleptic adverse effects, a high incidence of seizures, deaths in overdose (2), and the possibility of long-term neurological damage. Amoxapine is less potent than other tricyclic antide-pressants, with a therapeutic dosage range of 75600 mg day (usually 200-400 mg day). Clinical effects have not been consistently correlated with plasma concentrations, but amoxapine has similar efficacy to other tricyclic antidepressants in heterogeneous populations of depressed patients. Controlled comparisons have shown that its clinical profile is very similar to that of imipramine (3) and that it is somewhat less sedative than amitriptyline (4-6). In two of these studies (4,6) the results confirmed the suggestion of a somewhat earlier onset of action. Amoxapine appears to have the...

Drug Selection for the Treatment of Major Depression With Psychotic Features

Clear psychotic symptoms, such as delusions or hallucinations, are observed in approximately 25 of patients with major depressive disorder. These symptoms often respond poorly to antidepressants when they are administered alone, and usually require the use of adjunctive antipsychotic agents. Treatment can be initiated simultaneously, though many clinicians prefer to start the antipsychotic dose first and then add the antidepressant to the regimen. Though there are limited data on the adequate dose of antipsychotic for this group, most clinicians would recommend 5 to 10 haloperidol equivalents. This group of unipolar depressed patients may be at the highest risk of TD thus the antipsychotic dosage should be tapered and then discontinued when the patient's psychotic symptoms remit.

TABLE 22 Various Uses of Antidepressants

Major Depression Acute depression Prevention of relapse Other depressive syndrome Bipolar depression Atypical depression Dysthymia Other Uses Tricyclic Antidepressants DRUG SELECTION AND INITIATION OF TREATMENT FOR MAJOR DEPRESSION On average, all antidepressants are equally effective. Without a personal or family history of response to a particular agent, side effects are the most influential factors when selecting treatment. Both longitudinal and cross-sectional factors should be considered when selecting an antidepressant for major depression

Older Antidepressants

Tricyclic antidepressants (TCAs) cause more overdose deaths than any other drug. That said, TCAs are among the most effective antidepressants. Some studies would assert that this family of antidepressants is more effective than the celebrated SSRIs (of which Prozac is a member). When Prozac was first tested for clinical use, it performed marginally better than placebos. During that same trial, in order to compare the performance of Prozac against a more classic antidepressant, a TCA (imipramine) was also administered to Tricyclic Antidepressants Imipramine, Desipramine, Nortriptyline, Doxepin, and Clomipramine Antidepressants depressed patients. Imipramine produced a much more robust effect in many different indices than Prozac and proved more effective at eradicating depressive thoughts and elevating overall mood than Prozac.

Recommendations for the Use of Antidepressants

All patients with acute major depression should be considered reasonable candidates for pharmacotherapy. 3. There is good evidence for the use of antidepressants for non-mood disorders as well, particularly the anxiety disorders. 3. Lieberman JA, Greenhouse J, Hamer RM, Krishnan KR, Nemeroff CB, Sheehan DV, Thase ME, Keller MB Comparing the effects of antidepressants consensus guidelines for evaluating quantitative reviews of antidepressant efficacy. Neuropsychopharmacology 2005 30(3) 445-460 5. Practice guidelines for the treatment of patients with major depressive disorder, Second Edition. In American Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders, Compendium 2004, American Psychiatric Publishing, Arlington VA, 2004

F32 Depressive episode

F32. 0 Mild depressive episode .00 Without somatic syndrome .01 With somatic syndrome F32. 1 Moderate depressive episode .10 Without somatic syndrome .11 With somatic syndrome F32. 2 Severe depressive episode without psychotic symptoms F32. 3 Severe depressive episode with psychotic symptoms F32. 8 Other depressive episodes F32. 9 Depressive episode, unspecified F33 Recurrent depressive disorder F33. 0 Recurrent depressive disorder, current episode mild .00 Without somatic syndrome .01 With somatic syndrome F33. 1 Recurrent depressive disorder, current episode moderate .10 Without somatic syndrome .11 With somatic syndrome F33. 2 Recurrent depressive disorder, current episode severe without psychotic symptoms F33. 3 Recurrent depressive disorder, current episode severe with psychotic symptoms F33. 4 Recurrent depressive disorder, currently in remission F33. 8 Other recurrent depressive disor- F33. 9 Recurrent depressive disorder, unspecified

Tricyclic Antidepressants and St Johns Wort

John's wort (hypericum extract LI160) for at least 2 weeks in 12 depressed patients decreased the AUC between 0 and 12 h) of amitriptyline by 22 and nortriptyline by 41 . The AUC of all hydroxylated metabolites except 10-E-hydroxynortriptyline was also reduced. The mean peak concentration of amitriptyline was reduced from 69.8 to 54.1 ng mL in patients also receiving St. John's wort, and significant reductions were also observed in peak nortriptyline concentrations among subjects taking St. John's wort (43). The demethylation of amitriptyline to nortriptyline is catalyzed by CYP3A4 and CYP2C19, while further metabolism of nortriptyline through hydroxylation at position 10 is mediated by CYP3A4 and CYP2D6.

Pharmacology Antidepressants

It has long been known that antidepressants are also frequently effective treatments for anxiety disorders. The basic action of the majority of the antidepressants is to increase the availability of neurotransmitters in the synaptic cleft. The chemistry and pharmacokinetics of these agents are reviewed fully in Chapter 2. The most widely used antidepressants with anxiolytic properties are the SSRIs. These agents have the broadest spectrum of activity which spans the entire spectrum of DSM-IV-TR anxiety disorders. Other antidepressants with anxiolytic effects have different mechanisms of action. These include the inhibition of both serotonin and norepinephrine transporter sites (as seen with venlafaxine dosed above 150mg d, and with duloxetine and clomipramine) antagonism of the presynaptic alpha-2-adrenergic receptors (mirtazepine) and antagonism of postsynaptic serotonin type-2 receptors (nefazodone).

Tricyclic antidepressants

The use of both halothane and pancuronium in patients taking tricyclic antidepressant has been reported as resulting in severe tachydysrhythmias. Experiments in dogs have shown that this combination can produce ventricular fibrillation and cardiac arrest (56). Enflurane also resulted in tachycardias in dogs given both imipramine and pancuronium acutely, but not when the imipramine was given chronically for 15 days beforehand. Pancuronium should not be used in patients taking tricyc-lic antidepressants.

Tricyclic antidepressants in the treatment of enuresis

Although pediatric psychopharmacology is much neglected, nocturnal enuresis is an area of extensive research. An earlier review catalogued almost 100 publications on the topic (13). The tricyclic antidepressants have been shown to be effective in well-controlled trials, and over 40 publications had appeared before 1970. At that time adverse effects in children appeared to be minimal and comparable to those in adults. Since then considerable concern has developed over cardiotoxic effects and the risks of accidental overdose in children. The earlier reports have been summarized (SEDA-1, 10) managing overdose in children has been reviewed (SEDA-2, 10) death in a 16-month-old infant has been reported (SEDA-3, 9). Sudden death, possibly related to cardiac effects in children and adolescents, has been discussed (SEDA-15, 13) (SEDA-16, 9) (SEDA-18, 18) it was concluded that children taking tricyclic antidepressants require careful monitoring of the electrocardiogram, even when relatively low...

Pharmacotherapy of depressive disorders a consensus statement

The heads of centres collaborating with WHO in biological psychiatry and psychopharmacology decided to develop a series of consensus statements on key issues in biological research and treatment of psychiatric problems. This statement on Pharmacotherapy of Depressive Disorders is the first of the proposed series. Acute treatment Treatment of depressive disorders will be initiated with antidepressants. Practitioners should become familiar with the properties of two or three compounds, particularly with regard to the effective dose, The effective dose may vary from one population to another. In general, older patients need lower doses than younger ones. If a patient does not respond within 3 weeks, changing dosage or alternative medication should be considered. Electroconvulsive therapy may be considered in some cases of severe depressive illness and those not responding to treatment with antidepressant drugs and psychotherapy. Potential side-effects should always be discussed with the...

Teens and Antidepressants

Thirty to forty years ago, most mental health professionals did not believe that adolescents could experience true depression. At the time, a majority of psychiatrists still adhered to Freudian ideas of psyche. Under this doctrine, teenagers' minds were considered too immature to feel deep melancholy. Thus depression in adolescents was ignored or made light of as something that would go away in time that it was just a stage or hormones. Fortunately, in the last twenty years clinicians have come to realize that teenagers are especially at risk of developing major depression (Figure 7.1). Moreover, people who suffer from chronic depression often experienced depressive states early in their teens. If left untreated, periods of adolescent melancholy may impair the development of emotional maturity, increasing the risk of life-long depression. The above statistics show the percentage of depressed kids at a set point of time in America. However, if one were to analyze the percentage of...

Other antidepressants

Due to the quantity and the results of documented experience, St. John's wort or hypericin preparations and mirtazapine are acceptable during breastfeeding, If compellingly indicated, moclobemid, venlafaxine, and bupropion are also tolerable. Whenever possible, the drugs of choice among tricyclic antidepressants or SSRIs are preferable. In general, monotherapy should be the goal. In cases of symptoms potentially associated with the drug therapy, a pediatrician and a teratology information center should be contacted to decide individually upon measuring drug values in the infant's serum, supplementary formula feeding, weaning, and or changing the therapy. As with all psychoactive drugs, there is insufficient experience on the long-term effects on breastfed children of ongoing maternal therapy.

Antidepressants Elavil and Relatives

These drugs date from 1958, when the parent compound, imip-ramine (Tofranil), was invented. It is still in wide use today, along with a close relative, amitriptyline (Elavil), and a number of other similar drugs. Some depressed patients respond very well to these medications but not until after at least two weeks of regular use. On the other hand, the toxic effects begin right away sedation, dry mouth, blurred vision, constipation, difficulty in urinating. Normal people are likely to notice only these side effects without any positive mood changes. A newer antidepressant drug is fluoxetine (Prozac), unrelated to the older members of this group. It is currently very popular in psychiatric medicine. Fluoxetine is an effective antidepressant, but some patients cannot tolerate it, because it makes them very anxious. Like the major tranquilizers, the antidepressants do not lend themselves to recreational use because no one likes their effects. Often, even depressed patients who are helped...

Therapeutic Drug Monitoring of Antidepressants

Therapeutic Drug Monitoring of Antidepressants Therapeutic Drug Monitoring of Antidepressants lithium concentration between 0.8 and 1.2mmol L (134). Lithium therapy has various neurological, cardiovascular, and renal side effects. Serum lithium concentration of 3.5mmol L or higher is considered potentially lethal and hemodialysis therapy is recommended (135). More recently introduced antidepressants are selective serotonin reuptake inhibitors (SSRIs), including citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline. This class of drugs has a flat dose-response curve, thus a wide therapeutic index. Currently, most investigators agree that therapeutic drug monitoring of these drugs in the majority of patients is not essential (136). The reference ranges and costs of monitoring antidepressants are listed in table 8.

Miscellaneous Antidepressants

The miscellaneous antidepressant drugs are contraindicated in patients with known hypersensitivity to the drugs. Among the miscellaneous antidepressants, bupropion and maprotiline are Pregnancy Category B drugs. Other miscellaneous antidepressants discussed in this chapter are Pregnancy Category C drugs. Safe use of the antidepressants during pregnancy has not been established. They should be used during pregnancy only when the potential benefits outweigh the potential hazards to the developing fetus. These drugs are used cautiously in patients with liver or kidney impairment and during lactation. The miscellaneous antidepressants are given with caution to patients taking alcohol or other CNS depressants.

Third Generation Antidepressants

Venlafaxine does not substantially inhibit the CYP enzyme, and is not highly protein-bound, thus it tends to have few clinically significant drug-drug interactions. Duloxetine is metabolized by 1A2 and 2D6 P450 isoenzymes, and may increase plasma levels of other antidepressants, antipsychotics, and Type 1C antiarrhythmics, such as flecainide (Tambocor). Nefa-zodone is highly protein-bound, and has several active metabolites. It is also a strong inhibitor of CYP3A4, and affects other drugs also metabolized by that pathway however, it has little affinity for the CYP2D6 enzyme. Mirtazapine is highly protein-bound as well, but appears to only weakly affect the cytochrome enzymes.

Tricyclic and tetracyclic antidepressants

Tricyclic antidepressants (TCAs) inhibit the reuptake of the neurotransmitters, noradrenaline and serotonin, in the adrenergic neurones, which results in increased concentrations of those neurotransmitters at the receptor. Maternal exposure to antidepressants may be associated with a risk for spontaneous abortions. However, the underlying depression could also be a contributing factor (Hemels 2005). Kall n (2004) reports an increased risk for preterm birth and low birth weight.

Nontricyclic antidepressants

After discovery of TCAs and monoamine oxidase inhibitors, collectively called first-generation antidepressants, many other classes of antidepressants were discovered. These include amoxapine and maprotiline that affect reuptake of monoamines similar to secondary amine TCAs. Trazodone is a weak inhibitor of serotonin reuptake but has little effect on norepinephrine uptake. Bupropion inhibits reuptake of norepinephrine and dopamine. In addition to its use as an antidepressant, bupropion is used as an aid to stop smoking. Venlafaxine and mirtazapine are other non-TCAs with novel properties of inhibiting both norepinephrine and serotonin. Their side effects profile is lower than that of TCAs (43). The other class of antidepressants called SSRIs has become the most widely prescribed group of antidepressants in the USA. In addition to inhibiting serotonin uptake, these drugs interact with serotonin receptors to cause pharmacological response. Advantages of SSRIs over TCAs include their lack...

Neurobiological Changes Induced By Chronic Administration Of Antidepressants

Bupropion Reeptor Profile

The actions of all the compounds described so far seem to underpin the monoamine hypothesis. Yet an outstanding problem in treating depression is that the therapeutic response is both slow and progressive a significant improvement usually takes at least 2-3 weeks and sometimes much longer. Obviously, if we are to explain the therapeutic effects of antidepressants, we must search for long-term neurochemical changes that occur after their prolonged administration. The first indication that some neurochemical changes developed only after prolonged treatment with antidepressants came from landmark experiments carried out by Vetulani and Sulser in the mid-1970s (Vetulani et al. 1976). They found that repeated, but not a single, administration to rats of any of the antidepressants which were available at that time (i.e. MAOIs, TCAs, iprindole and even simulated electroconvulsive therapy) attenuated the increase in cAMP in the cerebral cortex induced by -adrenoceptor agonists. They suggested...

Antidepressants

The use of antidepressants in the treatment of depression remains the best-understood use of these medications however, there is a growing list of other indications for antidepressants, including panic disorder (PD), obsessive-compulsive disorder (OCD), bulimia and posttraumatic stress disorder (PTSD). Many of these illnesses respond best to combination treatment modalities that include medication and various forms of psychotherapy. Within the past 25 years, similarly efficacious tricyclic and heterocyclic antidepressants have been developed but with varying side-effect profiles. A new direction in antidepressant pharmacology began in 1987 with the discovery and In evaluations of the many antidepressants available, the focus has generally been on the agent's side-effect profile and ease of administration. Despite many efforts in this area, there is no conclusive evidence to demonstrate the clinical superiority of any one group of agents.

Monoamine Oxidase Inhibitors Isocarboxazid Phenelzine Tranylcypromine Selegiline Moclobemide

Tricyclic Antidepressant Diagram

Monoamine oxidase inhibitors (MAOIs) are less commonly prescribed than TCAs. Their use is one of last resort, when no other drugs can cure a patient's depression. As with TCAs, MAOIs are quite effective in curing patients experiencing severe depression and also atypical depression. Depression is termed atypical when an affected person sleeps more than normal and gains weight, the opposite effects of more commonly experienced depressive behavior such as insomnia and weight loss. Other depressive symptoms such as extreme fatigue during the day and feelings of hopeless and worthlessness are seen in both kinds of depression. by a certain type of serotonin receptor (5-HT1A). Since the brainstem modulates cardiovascular and breathing functions, an overload of serotonin in the brainstem may potentially cause hypertension. Because of this, stimulants such as methylphenidate (Ritalin ), dopamine, epinephrine, and norepinephrine, or other antidepressants such as SSRIs or TCAs should be avoided...

Introduction History and Brain Basics

At one time or another, almost every teen may appear to be depressed. Usually, the depression is slight and goes away with time. But some kinds of depression need medical intervention. With such an intervention, writing a prescription for Prozac or some other antidepressant drug (Figure 1.1) has become the first order of business. Yet, less than twenty years ago, adolescents were rarely diagnosed as depressed, much less given antidepressants. Today, however, teenagers are now receiving medications almost routinely for symptoms that can hardly be termed depressive attention deficit disorder, social anxiety, or drug addiction, for example. Thanks to the Prozac revolution of the 1980s and 1990s, a majority of people in America know someone who has used antidepressants. Over 34 million people in the United States have been issued prescriptions for Prozac or another selective serotonin reuptake inhibitor (SSRI). In other words, one American in ten has used Antidepressants in Common Use...

Venlafaxine Mirtzapine Bupropion Trazodone Nefazadone

Ssri Diagram

Second generation antidepressants encompass al of the chemically unrelated drugs which were developed in the wake of Prozac's success. This diverse collection has been grouped together mostly because they do not operate as selective serotonin reuptake inhibitors. Instead, each one interacts differently with neurotransmitters that are tied to depression serotonin, norepinephrine, or dopamine. For instance, one of the more popular non-SSRIs, Effexor (venlafaxine), selectively inhibits the uptake of serotonin and norepinephrine, acting on the same molecular machinery as tricyclic antidepressants (TCAs). But, in contrast to TCAs, Effexor shows no affinity for other neurotransmitter receptors and thus has far fewer side effects than the Figure 4.1 Second generation antidepressants, some of which are listed here, have the fewest side effects of drugs for depression treatment. Except for Amoxapine and Venlafaxine, the incidence of sexual dysfunction is very low, compared to the high...

Fluoxetine Sertraline Paroxetine Citalopram Fluvoxamine

Drug Sertraline Mechanism Action

The SSRIs were the first family of antidepressants not discovered by chance. Their development was planned according to what was known about the neurochemistry of depression, which partially explains their lack of side effects and efficacy of action. David Wong, an antibiotics researcher at Eli Lilly, had just learned a new technique that allowed him to measure uptake of chemical messengers (neurotransmitters) in neurons. Since Wong knew that current antidepressants' side effects (such as those seen in tricyclics) were mostly due to norepinephrine uptake rather than serotonin, he decided to look for compounds that would alter serotonin uptake only, in hopes of developing a drug that would cure depression but not cause the undesirable side effects associated with the earlier classes of antidepressants. After experimenting with several obscure compounds, Wong found that a tri-fluoridated (containing three fluoride atoms) molecule called fluoxetine had the most specific serotonin uptake...

Most Parents Dont Know If Their Teen Is Depressed

Obesidad Sobrepeso Quotes

Although parents seem to have tunnel vision when it comes to the moods of their children, most were reported to be fairly open to treating depression with antidepressants. Almost ten years later, the subjects, now adults in their twenties, were questioned about depressive symptoms and rate of drug use. Of these subjects, 8.3 percent were given unipolar depression diagnoses. Furthermore, 5.2 percent were alcohol dependent, and 6.1 percent used illicit drugs. Heavy alcohol, marijuana, and other illicit drug use were all correlated to major mood disorders. Over 80 percent of the depressed subjects had histories of marijuana use during adolescence and 66 percent reported illicit drugs use. The difficulty in resolving these opposing arguments is that there are very few clinical studies which track the safety and efficacy of many new antidepressants currently prescribed for teenagers. In fact, many of these antidepressants are not officially mandated for use in adolescents. What's more,...

Lithium And Conduct Disorder

Lithium has unique properties as a treatment for manic depression, but it is by no means the only treatment. Other mood-stabilizing drugs are also prescribed for treatment of the manic phase of the disorder. These drugs are often anti-convulsants such as Depakote (valproate) or sometimes antipsychotic drugs such as Zyprexa (olanzapine). As these drugs are not traditionally thought of as antidepressants, they will not be discussed in detail. Antidepressants commonly used for unipolar depression are also effective in treating the depressive stage of bipolar disorder. Often antidepressants such as SSRIs are prescribed in conjunction with lithium to stave off manic highs as well as depressive lows.

Serotonin And Suicide

Easy Brain Diagram

Despite the hype of Prozac being the happy drug, people taking SSRIs do not feel high or especially jubilant. As with older antidepressants (TCAs and MAOIs), the most commonly reported side effect of SSRIs is jitteriness (Figure 3.2). People have likened the short-term effects of Prozac to that of highly caffeinated beverages. Indeed, as with too much caffeine, nausea and slight headache are associated with these drugs. However, it must be noted that caffeine has an undefined and most likely negligible effect on the serotonin system. Yet Mayberg's finding does not imply that females are not receiving the same benefits from Prozac as males. On the contrary, Eli Lilly was recently given FDA approval to sell Prozac as a cure for premenstrual dysphoric disorder (PMDD) under a new name Sarafem. This marketing move was done partially to license a new patent for Prozac, whose license as an antidepressant had expired. However, studies have shown that Prozac does appear to relieve some of the...

Psychological psychiatric

The short-term occurrence of depressive symptoms has been investigated by using the Montgomery and Asberg Depression Rating Scale (MADRS) before and after 3 and 5 days of treatment in 48 patients without a previous psychiatric history and treated for renal cell carcinoma or melanoma with aldesleukin alone (n 20), aldesleukin plus interferon alfa-2b (n 6), or interferon alfa-2b alone (n 22) (44). On day 5, patients in the aldesleukin groups had significantly higher MADRS scores, whereas there were no significant changes in the patients who received interferon alfa-2b alone. Eight of 26 patients given aldesleukin and only three of 22 given interferon alfa-2b alone had severe depressive symptoms. Depressive symptoms occurred as early as the second day of aldesleukin treatment and were more severe in the patients who received both cytokines. Early detection of mood changes can be useful in pinpointing patients at risk of subsequent severe neuropsychiatric complications.

Diagnoses in Psychiatric Disorders

Bipolar Disorder The syndrome of bipolar disorder was first noticed in the 1800s. It was given the name manic-depressive illness because extended periods of depression, with its attendant lethargy, dysphoria, hopelessness, tearfulness, poor appetite, and suicidal thoughts, alternate with extended periods of manic symptoms of elation, grandiose thinking, rapid speech, accelerated thoughts, and hyperactivity. Sometimes manic thinking can include hallucinations and delusions. There are often extended periods of normal mood and good functioning.

The Chemical Imbalance Theory

As technology improved, our understanding of how these medicines worked in the brain grew tremendously. New theories of psychiatric problems emerged based on how the medicines worked. For example, it appeared that the effect of Thorazine was due to its ability to block the effects of dopamine, a neurotransmitter important to brain function (see Appendix A). This gave rise to the theory that schizophrenia was caused by an excess of dopamine, commonly termed the dopamine hypothesis. Researchers proposed that depression was due to a deficit in norepinephrine, the catecholamine hypothesis, based on the knowledge that different antidepressants raised levels of norepinephrine in the brain. Lithium fixed the highs and lows of Bipolar Disorder, which perhaps was caused by a periodic excess or deficiency of a brain chemical. All the theories proposed an excess or a deficiency of a brain chemical, that is, a chemical imbalance.

Organs and Systems Liver

Of all the tricyclic antidepressants, amineptine appears to be the most likely to cause liver damage. More than 26 cases of toxic hepatitis have been reported in France (6). In most cases, hepatitis occurred within the usual dosage range and recurred on rechallenge. However, in several instances it was reported after overdosage. There are other reports of hepatotoxicity associated with aminep-tine (7,8).

Drug Administration Drug overdose

A bleak picture has rapidly evolved for amoxapine with regard to its toxicity in overdosage. Over 18 months, 33 cases were reported from Washington, DC, and New Mexico Poison Centers (2). These cases included 5 patients who died and 12 who developed seizures. Thus, the mortality rate of 15 greatly exceeds that of 0.7 for other antidepressants in the same centers, and the seizure rate is 36 compared to 4.3 . The authors noted that the striking CNS toxicity of amoxapine overdose with frequent, persistent, and poorly controlled seizure activity is disconcerting.'' In a retrospective comparison of deaths from antidepressant overdosage in Scotland, England, and Wales between 1987 and 1992, the number of deaths per million prescriptions of amoxapine was significantly higher than expected (13).

Long Term Effects Drug abuse

There is a persistent illegal market in androgenic anabolic steroids, to promote physical strength. A difficulty in determining the ultimate consequences of anabolic steroid abuse for body-building or to advance sporting achievement is that individuals who are susceptible to such abuse may well have taken several different types of substance at the same time or in succession. Indeed, an analysis of the hair of seven body-builders showed what the authors termed a complete pharmacopeia'' of drug residues, ranging from glucocorticoids, anabolic steroids, and androgens to beta-adrenoceptor agonists, antidepressants, diuretics, and human chorionic gonado-tropin (49).

Create Your Treatment Plan

Compare Treatments Compare the treatments with the benefits that you hope to derive from medication. Although it may seem that taking a pill is the simplest alternative, often this is not so. For example, antidepressants for depression can seem very straightforward. People who jump right into them, pay a couple of hundred dollars a month, and then find their sexual lives severely curtailed begin to re

General Information

The newer antidepressants that have followed the monoamine oxidase inhibitors and tricyclic antidepres-sants are listed in Table 1. Most of them are covered in separate monographs. They have a wide variety of chemical structures and pharmacological profiles, and are categorized as second generation'' antidepressants purely for convenience. Although these drugs are widely considered to be as effective as each other and as any of the older compounds, they have different adverse effects profiles. No new antidepressant has proven to be sufficiently free of adverse effects to establish itself as a routine first line compound some share similar adverse effects profiles with the tricyclic compounds, while others have novel or unexpected adverse effects. Complete categorization of each compound will rest on wide-scale general use beyond the artificial confines of clinical trials. This also includes the experience that accumulates from cases of overdosage, which cannot be anticipated before a...

Chlorphenamine Chlorpheniramine Teldrin Trimeton

- Risk of increased sedation when combined with alcohol and drugs acting on the central nervous system opioid analgesics, neuroleptics (chlorpromazine, haloperidol, etc.), other antihistamines (chlorphenamine), antidepressants (clomipramine, fluoxetine, etc.), phenobarbital, etc.

The Flinders Sensitive Rats

At Flinders University in Australia, two other lines of rats were developed in the late 1970s (Overstreet et al. 1979) by selective breeding for differences in the hypothermic response to the cholinesterase inhibitor diisopropylfluo-rophosphate. This approach aimed at reversing the order of questions asked by typical selective breeding programs it chose a physiological response to specific pharmacological agents as the selection criterion. Only afterwards did behavioral alterations enter the evaluation in order to identify possible anxiety-related or depressive-like characteristics. From a number of various findings it was concluded that the Flinders sensitive line, being hypersensitive to cholinergic agonists, may rather represent an animal model of depression more than anxiety disorder, because these rats exhibit several symptom patterns of depression, such as reduced locomotor activity, reduced body weight, increased rapid eye movement (REM) sleep, and cognitive (learning) deficits...

Serotonin Receptor 1A

The 5-HT1A receptor subtype has long been implicated in the pathophysiology of anxiety and depression its role as a molecular target of anxiolytic and antidepressant drugs is well established (Griebel 1995 Griebel et al. 2000 Olivier et al. 1999). Patients with panic disorder and depression display an attenuation of5-HT1A receptor-mediated hypothermic and neuroendocrine responses, reflecting a reduced responsivity ofboth pre- and postsynaptic 5-HT1A receptors (Lesch et al. 1990b Lesch et al. 1992). Likewise, a decrease in 5-HT1A ligand binding has been shown in postmortem brain of depressed suicide victims (Cheetham et al. 1990) as well as in forebrain areas such as the medial temporal lobe and in the raphe of depressed patients elicited by positron emission tomography (PET) (Drevets et al. 1999 Sargent et al. 2000). Both glucocorticoid administration and chronic stress, a pathogenetic factor in affective disorders, have also been demonstrated to result in downregulation of 5-HT1A...

The Serotonin Syndrome

The use of MDMA triggers an excess release of serotonin (McKenna and Peroutka 1990 Rudnick and Wall 1992), which can cause the serotonin syndrome, one of the more serious complications associated with Ecstasy use. This syndrome is a rare, drug-induced event characterized by confusion, difficulty walking, increased sweating, diarrhea, heightened deep tendon reflexes and myoclonus (muscle jerks), poor control of heart rate and blood pressure, shivering and increased muscle tone and rigidity, which can lead to hyperthermia and death (Sternbach 1991 Ames and Wirshing 1993). This syndrome carries a mortality rate of about 10 to 15 percent. Drugs known to affect serotonin metabolism include amphetamines, cocaine, and many different kinds of antidepressants. The occurrence of serotonin syndrome as the result of Ecstasy use may explain some hyperthermic fatalities among patients who engaged in minimal physical exercise. However, since muscle rigidity, a common feature of serotonin syndrome,...

And Antiretroviral Drugs

Immunoassays are commercially available for TDM of antiasthmatic drugs theophylline and caffeine. The manufacturer of the FPIA assay for determination of total tricyclic antidepressants (TCA) in serum only recommends this assay for screening of TCA in serum in a patient with suspected overdose and cautions against using this assay for routine TDM of TCA. A patient overdosed with carbamazepine may show a falsely elevated TCA level if the FPIA assay is used because of cross-reactivity of carbamazepine with the antibody used in this immunoassay (39,40). Both HPLC and GC or GC combined with mass spectrometry can be used for routine TDM of various TCA. Methods for TDM of TCA are discussed in detail in Chapter 8. Recently, Wille et al. (41) reported HPLC and GC MS analysis of 13 new-generation antidepressants (venlafaxine, fluoxetine, viloxazine, fluvoxamine, mianserin, mirtazapine, melitracen, reboxetine, citalopram, maprotiline, sertraline, paroxetine, and trazodone) together with eight...

Other analytical techniques

Lithium has been used in the treatment of manic-depressive disorder since 1970, and the narrow therapeutic index of lithium with the nonspecific nature of lithium toxicity prompted routine therapeutic monitoring for these patients. Methodologies available for routine determination of lithium in human serum or plasma include flame atomic emission spectroscopy, flame atomic absorption spectroscopy, potentiometry

Adenylyl Cyclase Type VIII

Induced anxiety may be complex, involving impaired long-term depression (LTD) in the CA1 region of the hippocampus and failure to activate CRE-binding protein (CREB) in the CA1 region after restraint stress. Interestingly, it was recently reported that CREB1 polymorphisms predispose to depressive disorder in a gender-specific manner, further strengthening the assumption that this pathway is involved in emotion regulation (Zubenko et al. 2003).

Adverse Reactions

Reserpine is used cautiously in patients with a history of depression, in patients with renal impairment or cardiovascular disease, and during pregnancy and lactation. Guanethidine, another peripherally acting antiadrenergic drug, is con-traindicated in patients with pheochromocytoma and congestive heart failure. The drug is used cautiously in patients with bronchial asthma and renal impairment and during pregnancy and lactation. Anorexiants, haloperidol, the monoamine oxidase inhibitors, tricyclic antidepressants, and phenothiazines decrease the hypotensive effects of guanethidine.

Neurokinin 1 Receptor

Although substance P (SP) and its receptor, neurokinin 1 receptor (NK1R), have been implicated in the control of mood, anxiety, and stress, the efficacy of NK1R antagonists as both antidepressants and anxiolytics has been matter of considerable debate (Lesch 2001a). Santarelli and associates (2001) have recently made a strong argument for a critical role of the SP NK1R system the modu

The Building Blocks

Serotonin has reigned as the royal neurotransmitter for decades, and there's little sign of change. The new, safer, and more effective antipsychotic medications all have unique effects on serotonin. The new generation of antidepressants, of which Prozac is the most famous, also specifically modify the function of this neurotransmitter.

Introduction Understanding Endocrine Behavior Interactions Lessons from Mutant Mice

Anxiety disorders are common, and lifetime prevalence for the group of disorders is estimated to be as high as 25 (Kessler et al. 1994). These disorders display a substantial lifetime and episode comorbidity between each other and between other psychiatric conditions, particularly mood disorders (Hettema et al. 2001). With respect to the neuroendocrine phenotype, increased concentrations of corticotropin-releasing hormone (CRH) in the cerebrospinal fluid have been reported in stress-related clinical conditions (Holsboer 1999, 2003). In major depression, the combined dexamethasone (DEX) CRH test, in which DEX-pretreated subjects receive a single dose of CRH, has proved to be the most sensitive tool for the detection of altered hypothalamic-pituitary-adrenocortical (HPA) regulation. Depending on age and gender, up to 90 of patients with depression show this neuroendocrine phenomenon (Heuser et al. 1994). Panic disorder patients do not show any relevant alterations in their basal...

Treatment Options for Depression

Tricyclic antidepressants (TCAs) Heterocyclic antidepressants Tricyclic Antidepressants (TCAs) Named for their chemical structure, TCAs are the gold standard for treatment of depression because of their effectiveness. They need to be taken every day and take some weeks to work. They have been supplanted by other drugs, notably the SSRIs, because of their tendency to cause weight gain, dry mouth, constipation, sweating, and low blood pressure. Stimulants Named for the effect they produce, stimulants are most commonly used in the treatment of attention deficit disorder. They have been abused in the past by people who enjoy their ability to produce a burst of physical and mental energy. As a result, they are used infrequently for depression because so many other alternatives exist. Nevertheless, they can be effective antidepressants. Methylphenidate is the stimulant commonly employed. Although people notice improved energy right away, improvement in depression may take some weeks.

Miscellaneous Anticonvulsants

The miscellaneous anticonvulsants are used cautiously in patients with glaucoma or increased intraocular pressure a history of cardiac, renal or liver dysfunction and psychiatric disorders. When the miscellaneous anticonvulsants are used with other CNS depressants (eg, alcohol, narcotic analgesics, and antidepressants), an additive CNS depressant effect may occur.

Combination therapy

Of 656 Danish patients who were taking clozapine, 35 were taking concomitant neuroleptic drugs, 28 benzodiazepines, 19 anticholinergic drugs, 11 antidepressants, 8 antiepileptic drugs, and 2 lithium (15). The rationale for supplementing clozapine treatment in refractory schizophrenia in this way has been thoroughly reviewed following a bibliographic search covering 19781998 (16). In all, 70 articles were retrieved but only a few were controlled studies, most being case reports series. Among the many possible drug combinations, the evidence suggests that clozapine plus sulpiride is the most efficacious combination. The combined use of benzodia-zepines and clozapine can cause cardiorespiratory collapse valproate can cause hepatic dysfunction and more so with clozapine lithium can cause neurotoxicity and seizures and more so with clozapine and at least some serotonin reuptake inhibitors (SSRIs) appear to raise plasma clozapine concentrations to above the usual target range.

Syndromes of Depression and Their Treatment

Thyroid disorders, anemia, cancer, Alzheimer's disease, and Epstein-Barr virus infections can lead to depression, so you should consider a physical examination and appropriate laboratory work before starting treatment. Ideally, your depression will resolve when you obtain treatment for your medical problem, although you may require treatment with antidepressants indefinitely if you have Alzheimer's or Parkinson's disease. Acute Depression This form of depression generally occurs more abruptly, often following the death of a loved one, a physical injury or illness, or an unwanted change in your family or work. You are vulnerable to developing acute depression if you suffer from chronic depression or bipolar disorder. The symptoms of acute depression are generally more severe than in the milder chronic depression (which is why psychiatrists often call this major depression). How to Start Several antidepressants are first-line treatments, that is, they are the most likely to help you...

Combined Antidepressant Therapy

Open trials have supported the use of combined therapy of a TCA and a serotonin reuptake inhibitor in patients for whom either class alone has failed. When antidepressants are combined, it is important to remember that the serotonin reup-take inhibitors can potentiate TCA levels, and this should be monitored carefully. MAOIs have also been used in combination with TCAs, although this should be monitored closely given the risk of potential toxic interactions. Given the risk of a serotonin syndrome, MAOIs should not be combined with serotonin reuptake inhibitors. Bupropion is frequently added to an SSRI to enhance efficacy or to alleviate side effects such as decreased libido, fatigue, and sedation.

Changing to a New Agent

When the switch involves an MAOI, sufficient time must be given for medication clearance. Although seldom used, MAOIs may be very effective in patients not responsive to other classes of antidepressants. Generally, 10 to 14 days is required for clearance of TCAs and MAOIs. Fluoxetine requires a much longer period 6 weeks whereas sertraline and paroxetine require about two weeks when switching to an MAOI. Another alternative is changing from an SSRI medication to an SNRI. There is some evidence that SNRIs may lead to higher rates of response and remission than SSRIs.

Monoamine Oxidase Inhibitors

The most common drug interaction with antidepressants is their influence on the metabolism of other drugs. Antide-pressants are metabolized through catabolic enzymes located in a variety of places, but primarily in the smooth endo-plasmic reticulum of hepatocytes the cytochrome P450 (CYP) enzymes. Many other drugs are also metabolized through similar pathways it is estimated that about half of all drugs prescribed depend on CYP for their metabolism. Of these enzymes, most drugs are metabolized by the enzymes CYP3A4 (50 ) and CYP2D6 (20 ). Other clinically important CYP enzymes include CYP2C9, and CYP2C19 and CYP1A2, the latter which is found in the brain and may affect CNS distribution of antidepressants. A list of the enzymes and some drugs commonly affected by them is found in Table 2-6. Tricyclic Antidepressants

Pharmacokinetic Effects

Absorption of TCAs can be inhibited by cholestyramine, which therefore must be given at different time intervals than the antidepressants. Specific substances reported to increase TCA levels include fluoxetine, antipsychotic medications, methylphenidate, and cimetidine. Methylphenidate has been combined with desipramine to treat attention deficits and depression in children. The combination therapy had a higher incidence of ECG changes (particularly higher ventricular rates), nausea, dry mouth, and tremor. Enzyme inducers that can lower tricyclic agent levels include phenobarbital and carbamazepine. The nicotine from cigarettes can also induce enzyme activity.

Treatment Options for Insomnia

Obtain an Evaluation There are three possible parts to a formal evaluation if your insomnia doesn't respond to improving your sleep habits. First, obtain a complete physical examination from your doctor to ensure that there is no medical condition that needs treatment. Second, evaluate the possibility that the insomnia is part of a depressive or anxiety syndrome that needs treatment. You will benefit from educating yourself about any disorder you may think you have and a consultation with a psychiatrist if you have symptoms that suggest an anxiety or depressive disorder. Finally, you may need an evaluation in a sleep laboratory to investigate the possibility that you have a primary sleep disorder. This commonly involves an overnight stay in a sleep laboratory at a hospital. Alprazolam (Xanax) Chlordiazepoxide (Librium) Clonazepam (Klonopin) Clorazepate (Tranxene) Diazepam (Valium) Estazolam (ProSom) Flurazepam (Dalmane) Lorazepam (Ativan) Oxazepam (Serax) Quazepam (Doral) Temazepam...

Treatment of Insomnia in Medical and Psychiatric Conditions

For prolonged stress that contributes to insomnia, antidepressants may make the most sense. Trazodone has fewer side effects than amitriptyline and is generally well tolerated. Many people don't find it effective, however. Medical Conditions Medical conditions obviously need appropriate treatment. Hyperthyroidism may take weeks to get under control when first diagnosed. Hypnotics or benzodiazepines may improve sleep and your quality of life while this is occurring. Cardiac and respiratory problems can impair sleep because they may interfere with the amount of oxygen you are getting. Obviously the primary medical problem needs to be treated. Pain may make it hard to sleep, and analgesics may not be enough help. Hypnotics and benzodiazepines may be helpful in the short run. If you experience chronic pain, antidepressants make a more sensible choice. The symptoms of panic disorder, generalized anxiety disorder, posttraumatic stress disorder, and obsessive-compulsive disorder are not...

High Risk Studies of Anxiety Disorders

Agor, agoraphobia Dep, depression Dx, diagnosis MDD, major depressive disorder OCD, obsessive-compulsive disorder Not eval, not evaluated. Agor, agoraphobia Dep, depression Dx, diagnosis MDD, major depressive disorder OCD, obsessive-compulsive disorder Not eval, not evaluated.

Drugs And Animal Research

Ecstasy-related visits to hospital emergency rooms have skyrocketed in recent years, with approximately 250 reports of Ecstasy-related emergencies in 1994 to more than 4,500 in 2000. The majority of the visits are Ecstasy-induced malignant hyperthermia, the risk of which is increased when Ecstasy is combined with other drugs such as LSD (candy flipping), psychedelic mushrooms (hippie flipping), methamphetamine (up Ecstasy), heroin (down Ecstasy), and cocaine, Rohypnol, cough syrup, and antidepressants.

State schedules USA Availability Prescription where legal

This quick-acting and long-lasting drug is widely used around the world for legitimate medical purposes. Flunitrazepam is prescribed to treat insomnia and anxiety, to relax muscles, to stop convulsions, and to calm people. In the 1990s it was Western Europe's most commonly prescribed calming and sleep-inducing medicine. The drug is administered to treat alcohol withdrawal syndrome, and experimental use in treating depression has found flu-nitrazepam promising. Some unauthorized use of the drug is believed to be for self-medication of depression and low self-esteem. The drug has specialized usefulness in surgery as a medication given prior to administration of anesthesia, and its tendency to reduce pressure inside the eyeball can avert the rise caused by the anesthetic succinylcholine (important if patients are at risk for glaucoma). In hospice care where doses can be higher and more frequent than normal, flunitrazepam has reduced nausea and vomiting from cancer chemotherapy.

How to Monitor Your Progress

Observe Physical and Psychological Changes It is important to notice all the various effects the medication has on you. If you notice any difficulties when you are taking medication in regards to your thoughts, feelings, behaviors or physical condition, it is important to bring this up with your doctor so that it can be addressed as effectively as possible. For example, antidepressants such as fluoxetine, paroxetine, and sertraline often cause significant sexual dysfunction. Even if your physician doesn't ask about it, bring it up so that you can discuss how you might handle it. Use Blood Levels as Servants, Not Masters Lithium, valproate, and many antidepressants and antipsychotics can be measured in the blood. Although therapeutic ranges for effective doses have been proposed, many people respond to levels that are above or below the supposedly therapeutic range. It is important to use blood levels as a guide to treatment, but not to believe them so blindly that you ignore the most...

Selective serotonin reuptake inhibitors SSRIs

SSRIs are equally effective but are better tolerated by some patients than TCAs. The SSRIs are also safer than other antidepressants for the mother and fetus in women with suicidal ideation. Fluoxetine is a long-acting SSRI. The half-lives of fluoxetine and the metabolite nor-fluoxetine are several days and 14 days, respectively. The half-life of citalopram is 36 hours fluvoxamine, paroxetine, and sertraline have half-lives of less than 24 hours. Maternal exposure to antidepressants may be associated with a risk for spontaneous abortion. However, the underlying depression could also be a contributing factor (Hemels 2005). Several investigators have found an increased incidence of preterm birth when SSRIs have been used throughout pregnancy or in the last half of pregnancy (Kallen 2004. Costei 2002, Simon 2002, Ericsson 1999, Chambers 1996, Goldstein 1995). Here, too, the underlying depression could be a contributing factor. In most studies, there was no control for the impact of...

How to Stop Medication

Taper Gradually You need to take into account the physical effects of withdrawal and the psychological changes you will experience. For example, benzodiazepines and antidepressants cause a variety of physical and emotional changes. These changes are far more easily tolerated when there has been a small decrease in the total amount you are taking rather than a complete cessation. Make sure your body has adapted to one change before you undertake another. In the case of some antidepressants, this may take months.

Review of Neuropsychological and Cognitive Data

Difficulties in attention and concentration as well as new complex verbal learning may be directly related, and must be understood in the context of not only these subjects' chronic cannabis use, but also their underlying chronic diseases and clinical syndromes, with attendant fatigue and preoccupation. Interestingly, depressive symptoms are not currently noted at a clinical level in any of the subjects despite their chronic medical conditions or long-term cannabis use. None displayed evidence of social withdrawal or apathy characteristic of the alleged amotivational syndrome. Rather, all were animated, engaging in conversation and demonstrating an active involvement with their ongoing care and the current research.

Organs and Systems Cardiovascular

In general, SSRIs are assumed to be safe in patients with cardiovascular disease, although there have been few systematic investigations in these patients. In a prospective study of 27 depressed patients with established cardiac disease, fluoxetine (up to 60 mg day for 7 weeks) produced a statistically significant reduction in heart rate (6 ) and an increase in supine systolic blood pressure (2 ) (4). One patient had worsening of a pre-existing dysrhythmia and this persisted after fluoxetine withdrawal. These findings suggest that, relative to tricyclic antidepressants, fluoxetine may have a relatively benign profile in patients with cardiovascular disease. However, the authors cautioned that in view of the small number of patients studied, these findings cannot be widely generalized. The effects of fluoxetine (20 mg day for 12 weeks) on sitting and standing blood pressures have been reported (5). Fluoxetine modestly but significantly lowered sitting and standing systolic and...

And other psychoactive substances

.30 Organic manic disorder .31 Organic bipolar disorder .32 Organic depressive disorder .33 Organic mixed affective disorder .23 Currently abstinent, but receiving treatment with aversive or blocking drugs .24 Currently using the substance active dependence .25 Continuous use .26 Episodic use dipsomania F1x.3 Withdrawal state .30 Uncomplicated .31 With convulsions F1x.4 Withdrawal state with delirium .40 Without convulsions .41 With convulsions F1x.5 Psychotic disorder .50 Schizophrenia-like .51 Predominantly delusional .52 Predominantly hallucinatory .53 Predominantly polymorphic .54 Predominantly depressive symptoms .55 Predominantly manic symptoms .56 Mixed F1x.6 Amnesic syndrome F1x.7 Residual and late-onset psychotic disorder

The Stigma of Addiction

Addiction is also said to occur with many sorts of activities and practices, like gambling, sex, or exercise. The idea that there can be distinct conditions of physical and psychological addiction remains controversial. For example, consider the occasional marijuana user who consumes the drug to steady himself and improve his occupational performance (a case to be discussed in chapter 6). In some sense, he is drawn to drug use by the nature of his work, but it is unlikely that he is physically addicted. A high-pressure executive may use Prozac or another antidepressant medication periodically to enable her to perform adequately in a position of authority, but it would seem odd to say that she is addicted to the drug. Yet it is not uncommon for both professionals and lay people to speak quite seriously about addictions to such things as television, exercise, or sex. In fact, addictions to sex and gambling are well-known and significant psychopatholo-gies, but neither addiction involves...

Observational studies

A wide range of persistent symptoms has been reported during interferon alfa treatment for chronic hepatitis C. An analysis of 222 patients from the USA and France, enrolled in a multicenter trial, suggested that pretreat-ment symptoms were an important predictor of moderate or severe (defined as debilitating) adverse effects during treatment with interferon alfa (4). Compared with baseline, the incidences of moderate and severe fatigue, myalgia, arthralgia, headache, dry eyes, and dry mouth increased significantly after 6 months. In each case, the development of these debilitating adverse effects was associated with the presence of that symptom at baseline. They were more often reported in patients who received interferon alfa daily than three times weekly, and in US than French patients, suggesting possible differences in cultural attitudes toward illness. There was also increased use of antidepressants during the 6-month survey.

Listy rudodreva koka Coca leaf

When given on a long-term maintenance basis, lithium can prevent both manic and depressive mood swings or can drastically reduce their severity. It can also suppress the psychotic features sometimes exhibited in manic-depressive patients. The drug's mode of action is unknown. Side effects of its use include increased urination, tremors, diarrhea, nausea, drowsiness, and, at higher concentrations, convulsions, coma, and death. Liticon Pentazocine or Pentazocine hydrochloride or Pentazocine lactate. Litiumkarbonat Lithium carbonate. Little D Colloquial term for Dilaudid. Little Green Friends Colloquial term for marijuana.

Cellular Mechanisms of Stress Induced Structural Plasticity

Chronic or severe stress is a well-known precipitant of some forms of anxiety and depressive disorders, and it is likely that stress-induced alterations in neuronal plasticity may underlie functional changes. Stress exposure in experimental animals can result in dendritic remodeling and atrophy in hippocampal CA3 pyramidal neurons (Margarinos et al. 1996 Sousa et al. 2000 Watanabe et al. 1992) as well as decreased hippocampal volume and neurogenesis (Czeh et al. 2001 Gould et al. 1997). These findings, along with observations of decreased hippocampal volume seen clinically in association with PTSD and depression (Bremner et al. 1995 Sheline et al. 1996), and the observation that clinically effective antidepressant treatments can reverse stress-induced changes in neuronal structure (Magarinos et al. 1999), have suggested the potential relevance of stress-induced structural alterations to affective disorders (Duman et al. 2000 Manji et al. 2001 Nestler et al. 2002).

Intracellular Signal Transduction Pathways in the Treatment of Anxiety

The most commonly prescribed treatments for anxiety are benzodiazepines and antidepressants. These therapeutic agents have very different mechanisms of action, time course of effect and side effect profiles. Benzodiazepines enhance the responsiveness of GABA, the major inhibitor neurotransmitter in the brain, by binding to the GABA benzodiazepine (GABA BZ) receptor complex. This results in rapid anxiolytic activity in rodent models and in humans, but can be accompanied by sedation. Antidepressants most often used for anxiety include the serotonin selective reuptake inhibitors (SSRIs), which block the serotonin (5-HT) transporter and increase synaptic levels of this monoamine. However, the therapeutic action of antidepressants for the treatment of anxiety, as well as depression, requires several weeks and sometimes months. This has led to the widely held hypothesis that adaptations, or neural plasticity changes, to the acute elevation of 5-HT are necessary for a therapeutic effect....

Intracellular Pathways Regulated by Antidepressant Treatment

Early studies to identify the long-term adaptations that underlie the actions of antidepressant treatment were focused on alterations in levels of monoamine receptors and transporters. This work has provided useful information demonstrating that multiple 5-HT and NE receptor subtypes are regulated by antidepressant treatment, presumably as a result of elevated synaptic levels of these monoamines. More recent studies have examined adaptations of intracellular signal transduction cascades that could represent common targets for antide-pressants. This section will review the work on the cAMP and Ca2+ signaling pathways and how these pathways could contribute to the anxiolytic actions of antidepressants. This is not meant to be a comprehensive review of the intra-cellular pathways regulated by antidepressants, but is a focused discussion of these signaling cascades, which to date have received the most attention. It is very likely that there are many other pathways that are regulated by...

Drug Selection Dose And Initiation Of Treatment

The major initial choice in treatment of anxiety disorders is the class of medication. Initiation of treatment, dosage titration, and continuation of treatment as well as discontinuation depend on medication class (see Table 4-2). Even within a medication class (e.g., antidepressants), side effects may vary (see Table 4-4). Abuse liability, delayed onset of action, and probability of lethality in overdose may play a role in drug choice. Since anxiety disorders are often chronic, the long-term tolerability of medication is often another key factor in initial treatment choice. Generally single-agent treatment TABLE 4-4. Common Reported Side Effects of Antidepressant Medications

Ibogaine The Rain Forest Alkaloid

Ibogaine, the principal alkaloid of the African rain forest shrub Tabernanthe iboga (Apocynaceae family), is currently being evaluated as an agent to treat psychostimulant addiction.227 Anecdotal reports of ibogaine treatments in opiate-dependent or cocaine-dependent humans describe alleviation of drug craving and physical signs of opiate withdrawal after a single administration of ibogaine, which in some subjects contributes to drug-free periods lasting several months thereafter. This has recently been confirmed in a preliminary study reporting that ibogaine significantly reduced craving for both cocaine and heroin and significantly improved depressive symptoms in an inpatient detoxification setting.228 In drug self-administration studies, ibogaine and related iboga alkaloids reduced intravenous self-administration of cocaine 1 h after treatment. This suppression on cocaine intake was evident 1 day later, and in some rats a persistent decrease was noted for as long as several...

Clinical Features of Depression

Symptoms of a major depressive episode usually develop over days or weeks. The primary diagnostic requirements are either a depressed mood or the loss of interest or pleasure in nearly all activities for at least two weeks. These symptoms must exist for most of the day and for nearly every day Five or more of the following symptoms also must be present during that same two-week period of time, and they must represent a change from previous functioning Periods of sadness are inherent aspects of the human experience, and they should not be diagnosed as a major depressive episode. The symptoms that are present must cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Symptoms must not be due to the direct physiological effects of a substance, such as a drug or medicine, or to a medical condition. The symptoms are not better accounted for by bereavement after the loss of a loved one (American Psychiatric Association 1994)....

Biochemical Basis of Depression

It is significant that many of the drugs prescribed for treatment of depression have serotonergic activity. The newest class of antidepressants, the serotonin reuptake inhibitors (Prozac, Zoloft, Paxil, Celexa, and others) and, to varying degrees, the tricyclic antidepressants prevent the recycling of serotonin back into presynaptic nerve endings. Monoamine oxidase (MAO) inhibitors prevent the breakdown of serotonin by the enzyme MAO. In either case, more serotonin is available for binding to receptors (Spiegel and Aebi 1983). The specific mechanism of action of these drugs, however, is still not clear.

Methyltertbutylether and monoctanoin 2313

Methylphenidate augmentation of citalopram in elderly depressed patients. Am J Geriatr Psychiatry 2001 9(3) 298-303. 55 Flemenbaum A. Hypertensive episodes after adding methyl-phenidate (Ritalin) to tricyclic antidepressants. (Report of three cases and review of clinical advantages.) Psychosomatics 1972 13(4) 265-8.

Basal HPA Hormone Levels in PTSD

The first report on cortisol levels in PTSD was that of Mason et al. who found that the mean 24-h urinary excretion of cortisol was significantly lower in combat Vietnam veterans with PTSD compared to psychiatric patients in four other diagnostic groups (Mason et al. 1986). The authors noted surprise at the fact that cortisol levels were low, since certain clinical features such as depression and anxiety in PTSD might have been expected to be associated with increased activity of the pituitary-adrenal cortical system. Since this initial observation, the majority of the evidence supports the conclusion that cortisol alterations in PTSD are different from those observed in acute and chronic stress, and major depression, but more importantly, that the HPA axis appears to be regulated differently.

Prescription Medications

Of sedating antidepressants (e.g., trazodone) as sleep aids, is common clinical practice. The melatonin agonist ramelteon, the most recently FDA-approved hypnotic in the US, is an agent with unique mechanism of action. The pyrazolopy-rimidine indiplon, not yet available in the US, is also a non-BZD GABA A modulator with promising side-effect profile. Other pharmacological options, limited to a few well-defined conditions with many caveats, include anticonvulsants (e.g., gabapentine, valproate, tiagabin) and antipsychotics (e.g., haloperidol, quetiapine).

Organs and Systems Psychological psychiatric

Some patients appear to develop manic symptoms in response to some antidepressants but not to others. Psychosis was reportedly triggered by mirtazapine in a patient taking long-term levodopa (2) and in another patient hypomania occurred. A 45-year-old woman had a long history of dysthymia and depression. She had taken many antidepressants, including tricyclics, SSRIs, amfebutamone, and venla-faxine. She had no history of mania or hypomania. She took sertraline 250 mg day, with only a transient response, and mirtazapine 15 mg day was added. Within 4 days she developed clear symptoms of hypo-mania, with euphoric mood, mild grandiosity, pressure of speech, increased energy, and a reduced need for sleep. Mirtazapine was withdrawn and sertraline continued within 3 days the hypomanic symptoms had remitted. The depressive disorder then re-emerged (3). Unlike most other antidepressants, mirtazapine does not inhibit the reuptake of monoamines, but instead blocks inhibitory a2-adrenoceptors. It...

MDMAs Role in the Treatment of Depression

In any case, MDMA's use in psychotherapy to stimulate positive feelings, such as openness and empathy, would seem to recommend it for a possible clinical role in treating depression. Riedlinger (1985) first proposed this in a discussion of MDMA's positive isomer activity and consequent release of serotonin in the brain. Because it is a potent releaser of serotonin into the synapse, and because of its short duration of effect, MDMA seems to be both effective and efficient as a drug for the medical treatment of depression. It works to enhance serotonergic function and mood in a matter of hours instead of weeks (as is the case for most prescription antidepressants), and it is effective when administered infrequendy, perhaps in weekly or monthly dosing intervals. This compares favorably to the multiple daily dosing required for most of the currendy available drugs that can be prescribed for treating depression (such as tricyclic antidepressants, MAO inhibitors, serotonin reuptake...

Susceptibility Factors Age

Because of the concern expressed about the use of tricyc-lic antidepressants in elderly people, MAO inhibitors have been studied in this population (39). Patients with dementia benefited in mood (but not cognition), and some non-demented patients also improved. Adverse effects were considered less frequent or troublesome than those due to tricyclic compounds, although one patient taking tranylcypromine became paranoid and another taking phenelzine developed a choreiform movement disorder. The fact that MAO concentrations increase with age supports the use of these drugs in the elderly, but their hypotensive effects and interactions with other drugs and foods suggest that they should be used with extreme caution in people who are exposed to poly-pharmacy and whose comprehension of and attention to warnings may be impaired.

Glucocorticoid Receptors in PTSD

Lymphocyte and brain GRs have been found to share similar regulatory and binding characteristics (Lowy 1989). A greater number of 8 00 a.m., but not 4 00 p.m., mononuclear leukocytes (presumably lymphocyte) type II GRs was reported in Vietnam veterans with PTSD compared to a normal comparison group (Yehuda et al. 1991b). Subsequently, Yehuda et al. reported an inverse relationship between 24-h urinary cortisol excretion and lymphocyte GR number in PTSD and depression (i.e., low cortisol and increased receptor levels were observed in PTSD, whereas in major depressive disorder, elevated cortisol and reduced receptor number were observed) (Yehuda et al. 1993a). Although it is not clear whether alterations in GR number reflect an adaptation to low cortisol levels or some other alteration, the observation of an increased number of lymphocyte GRs provided the basis for the hypothesis of an increased negative feedback inhibition of cortisol secondary to increased receptor sensitivity (Yehuda...

Organs and Systems Nervous system

Nefazodone is unusual amongst antidepressants in that it does not reduce and in fact may increase rapid eye movement (REM) sleep or dream sleep. In a controlled study in depressed patients nefazodone 400 mg day increased REM sleep, while fluoxetine 20 mg day produced the opposite effect (3). In addition, nefazodone increased sleep efficiency, while fluoxetine reduced it. The patients' subjective assessments of sleep improved more with nefazodone than with fluoxetine. However, the overall antidepressant effects of the drugs were similar. The function of REM sleep and its relation to depressive disorders is not clear, so it is uncertain whether preservation of REM sleep by nefazodone is likely to be of clinical consequence. antidepressants and SSRIs the estimated rate of adverse hepatic reactions was 1.28-4.00 per 100 000 patient years. However, the rate with nefazodone was much higher (29 per 100 000 patient years). This report supports concerns that nefazodone may be more hepatotoxic...

Drug Administration Drug formulations

Although mortality is generally low and infrequently associated with residual impairment (SED-13, 129), important exceptions occur when there is co-ingestion with alcohol, tricyclic antidepressants, or antiparkinso-nian agents. In acute overdosage of neuroleptic drugs alone, the most serious complications include shock, seizures, and cardiac dysrhythmias. These can be more problematic when the neuroleptic drugs are of low potency, for example thioridazine and chlorpromazine, but taken in high dosages.

Other Prescription Hypnotics

Small doses of sedating TCAs (e.g., amitriptyline, doxepin) are sometimes used as hypnotics. Patients with chronic pain may particularly benefit from this treatment strategy TCAs are frequently used to potentiate the benefits of traditional pain medications. They are potent inhibitors of REM sleep, and their discontinuation is often associated with REM rebound. Anticholinergic and adrenergic side effects and toxicity in overdose must be weighed against potential benefits. Mirtazapine is a newer sedating antidepressant that targets both the noradren-ergic and serotonergic systems. It may be a useful alternative to the tricyclic antidepressants as it is less anticholinergic and less toxic in overdose. Mirtazapine has strong antihistaminic activity that may cause significant weight gain with chronic use.

Pregnancy Category C

Animal and human experiments show that more pain relief can come from morphine if ephedrine is taken at the same time. Dextroamphetamine can improve pain relief provided by morphine. Alcohol, tri-cyclic antidepressants, and monoamine oxidase inhibitors (MAOIs, found in some antidepressants and other medicine) can boost morphine effects. Rat experiments indicate that benzodiazepine class depressants lengthen the effect from a morphine dose. Researchers find that morphine and nicotine have cross-tolerance in mice.

Putative Models of HPA Axis Alterations in PTSD

On the other hand, the model of reduced adrenal output accounts for why ambient cortisol levels would be lower than normal, and even for the relatively smaller magnitude of differences in ACTH relative to cortisol, but does not account for why basal ACTH levels are not significantly higher in PTSD than in comparison subjects, particularly in light of evidence of CRF hypersecretion. One of the challenge in elucidating a neuroendocrinology of PTSD is in being able to resolve the apparent paradox that cortisol levels are low when CRF levels appear to be elevated, as well as to accommodate a dynamic process in that accounts for observed diurnal fluctuations and potential responsivity to environmental cues. Heim et al. (2001) have again argued that in response to early trauma, CRF hypersecretion may result in a downregulation of pituitary CRF receptors leading to a decreased ACTH response. However, it is not quite clear according to this why in such cases CRF hypersecretion would lead to...

Peripheral Neuropathy

The pain arising from damage to peripheral nerves can be extremely difficult to control satisfactorily. Patients will commonly describe their pain as a constant burning, tearing or pricking sensation. Diabetic neuropathy is a good example and for some patients the use of tricyclic antidepressants or anticonvulsants is satisfactory. However, for others, these may be ineffective. Conventional analgesics are often of little use.

Cocaine Use and Related Toxicity in the United States

Completely new strategies for preventing the toxicity and abuse of cocaine are needed and novel methods may be best developed by employing modern biological and biochemical approaches (Jones 1992). It is unlikely that antagonists of neurotransmitter transporters or other pharmacological intervention (i.e., desipramine or other antidepressants) will be efficacious because the blood levels required to saturate the cocaine receptor will be too toxic in humans (Ritz et al. 1987) or have an induction period of several weeks (Fischman et al. 1990). The reasons for cocaine deaths probably stem partly from a contribution of the intrinsic toxicity and mechanism of action of cocaine and partly from the current lack of appropriate treatment for cocaine overdose. With heroin, the opiate receptor antagonist naloxone is likely to save someone brought to the emergency room with a heroin overdose. A comparable antagonist, such as the opiate antagonist naloxone, is currently not available to treat...

Current and Future Trends

Because of the limited success of NRT, smoking cessation research efforts are focusing more on non-nicotine medications. Several antidepressant and anxiolytic agents, as well as adrenergic and noradrenergic agents, were tested recently or are in clinical trials for this indication (170). There is emerging evidence that antidepressants and anxiolytics may be particularly helpful for subpopulations of smokers (i.e., those with mood disturbances). With the current trends in the smokers' population, anxiolytic and antidepressants will become increasingly important.

Family Genetic Factors

In another study, Lieb et al. (2002) confirmed the cross-aggregation of anxiety disorders and depression by showing that offspring of parents with depressive disorders have not only an elevated risk for depressive disorders but also for anxiety disorders. Considering parental comorbidity, the cross-aggregation between parental depression and general anxiety disorder in off- spring remained significant. These results are similar to the results of Kendler et al. (1997) who investigated the familial aggregation of mental disorders by using the family history data of the NCS. Although these researchers found some specificity in the familial transmission of generalized anxiety disorder, the cross-aggregation between major depression and generalized anxiety disorder remained stable after controlling for comorbidity. The influence of a family history of anxiety disorders on the risk to develop anxiety disorders was also demonstrated in several studies by using the family- and high-risk...

Comorbidity with Affective Disorders

Several population-based studies have consistently found a remarkable association between anxiety disorders and affective disorders, particularly with major depression (Weissman et al. 1994 Angst 1993 Lewinsohn et al. 1997 Merikangas et al. 1998 Regier et al. 1998 Kessler 2001). According to NCS data, subjects with an anxiety disorder have an almost five times greater chance of developing major depression, compared to subjects without any anxiety disorder (Kessler 2001). Cross-sectional studies that have investigated the temporal pattern of onset of anxiety and depression in comorbid cases have demonstrated that major depression generally develops secondary to anxiety, suggesting that anxiety disorders increase the risk for subsequent depression (Kessler et al. 1996 Regier et al. 1998). Recently, several prospective analyses of the EDSP study have shown that indeed almost all forms of anxiety disorders increase the risk for first onset of major depression (Wittchen et al. 2000a Stein...

Long Term Effects Drug withdrawal

In a study of the effects of sudden drug withdrawal in 34 patients taking phenelzine and 17 taking tricyclic antide-pressants who had been treated for a mean duration of over 9 months, depressed patients taking phenelzine had significantly more symptoms than depressed patients taking tricyclic antidepressants, and a third of them relapsed, compared with a quarter taking the tricyclic (9). At 3 months follow-up 47 of the patients taking phenelzine had resumed treatment compared with 23 taking the tricyclic. An attempt to distinguish between withdrawal symptoms and relapse on the basis of the rapidity and severity of symptoms was unsuccessful, but about a third

Treatment Systems and the Acceptance of Treatment

Response to some psychiatric disorders. At the turn of the last century, few clinicians thought of depression as a disorder instead, most believed it could be cured by simple motivation and, thus, few treatment resources were made available. Currently, almost all clinicians agree that clinical depression needs treatment. Perhaps the understanding of nicotine by administrators, clinicians, and the public in the 1990s is where the knowledge of depression was in the early 1900s.

Case 7 Drug Interactions between Prescription and Alternative Medications

After several days of inconclusive results, Mary Jo revealed to her physicians that she had been feeling a bit down due to all her medical problems. She had read about St. John's wort and its use to treat mild to moderate depression in a magazine. Intrigued, she had explored the findings by accessing several web sites and discovered that St. John's wort contains constituents that inhibit the reuptake of important neurotransmitters that regulate mood, similar to certain prescription antidepressants. She certainly did not want to take any more drugs, so she had thoughtfully investigated manufacturers, purchased a product standardized to contain 0.3 percent hypericin (the purported active ingredient), and carefully followed the dosing instructions on the label.

Drug Drug Interactions Fluoxetine

In the pharmacological management of patients with treatment-resistant depression, it is a common strategy to combine a drug that selectively inhibits noradrenaline re-uptake (for example reboxetine) with one that selectively inhibits the re-uptake of serotonin (for example an SSRI). As well as the hoped-for pharmacodynamic interaction, a kinetic interaction can also occur, because of the effect of SSRIs on CYP450 enzymes. The effect of combined treatment with reboxetine (8 mg day) and fluoxetine (20 mg day) has been compared with each treatment given alone for 8 days in 30 healthy volunteers in a parallel design (4). There was no potentiation of adverse effects by the combination. Fluoxetine increased the plasma AUC of reboxetine by 20 , but this was not statistically significant. The authors suggested that the combination of fluoxetine and reboxetine should have minimal adverse impact in depressed patients. However, the major metabolite of fluoxetine, norfluoxetine, is also an...

Placebocontrolled studies

In a 6-week open study of risperidone (mean dosage 4.7 mg day) in combination with mood-stabilizing treatments (usually lithium, carbamazepine, or valproate) for the treatment of schizoaffective disorder in 102 patients, 95 of whom completed the trial, at week 4 most patients had improved symptom severity and 9.3 were completely symptom-free (2). There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms, as measured by the UKU Side-Effect Rating Scale subscale for neurological adverse effects other adverse effects included depressive symptoms (n 13), exacerbation of mania (n 5), drowsiness (n 3), and impotence (n 2).

Barry Levine PhD and Rebecca Jufer Phipps PhD

In most healthcare facilities, toxicology laboratories have moved from a more general toxicology screen to a more limited screen. This limited screen will usually consist of a serum ethanol test by an enzymatic assay and a urine immunoassay screen for 5-10 drug classes based on commercially available immunoassay kits. These may be supplemented by serum tests for salicylate, acetaminophen, benzodiazepines and tricyclic antidepressants by immunoassay or spot tests. Although immunoassays are quite useful for rapid screening of many drugs, there are some limitations associated with this limited screening approach. This chapter discusses these limitations with regard to drug-facilitated sexual assault drugs, hallucinogenic amines, miscellaneous hallucinogens and opiates. One limitation is the fact that not all drug classes or drugs within a class are detected by these tests. In addition, some of the drugs discussed have very limited detection windows or exhibit instability that may limit...

Drug Administration

The SSRIs are in general considered to be less toxic in overdose than tricyclic antidepressants. From a review of cases of overdose with SSRI during 10 years it was concluded that SSRIs are rarely fatal in overdose when taken alone (62). In moderate overdoses of up to 30 times the daily dose, symptoms were either minor or absent. In higher doses, typical symptoms included drowsiness, tremor, nausea, and vomiting. At extremely high doses (over 75 times the usual daily dose), there were more serious toxic effects, including seizures, electrocardiographic changes, and disturbances of consciousness. When an SSRI overdose was taken in combination with alcohol or other drugs, toxicity increased, and almost all deaths involving SSRIs were in combination with other drugs.

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