Treatment Initiation And Dose Titration

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Once the questions above are answered, the clinician should select an antipsychotic medication and initiate the treatment trial. The algorithm from the practice guidelines for schizophrenia developed by the American Psychiatric Association may be useful for drug selection (Figure 1-1).

Selection of an agent in emergency settings for the management of the gross agitation, excitement, and violent behavior associated with psychosis might be based on clinical symptoms, differences in efficacy or side effects of candidate drugs, or, more pragmatically, the formulation of a drug as it affects route of administration, onset, and duration.

There is now a considerable amount of clinical experience with atypical antipsychotics in acute emergency situations, and they have come to replace first-generation antipsychotics as the agents of choice when treatment is initiated. Olanzapine and ziprasidone are available in short-acting formulations for intramuscular administration; risperidone and aripiprazole are available as oral solutions; and olanzapine and risperidone are available as rapidly disintegrating oral tablets. These various formulations provide tremendous flexibility to the clinician in choosing the optimal medication and method of administration based on clinical considerations.

The use of oral second-generation antipsychotics and benzodiazepines in combination is the most common medication strategy in psychiatric emergency settings. It is best to avoid combining antipsychotics in favor of sequential trials of monotherapy with different antipsychotics. Because most patients with schizophrenia will require long-term treatment with antipsychotics it is imperative that, in addition to short-term treatment goals of control of behavioral dysregulation

Psych Drug Monitoring

FIGURE 1-1. Somatic Treatment of Schizophrenia. Also refer to Table 1-1 and the following: First episode-Group(G) 2; Persistent suicidal ideation or behavior-G3; Persistent hostility and aggressive behavior-G3; Tardive dyskinesia-G2 all group 2 drugs may not be equal in their lower or no tardive dyskinesia liability and G3; History of sensitivity to extrapyramidal side effects-G2 except higher doses of risperidone; History of sensitivity to prolactin elevation-G2 except risperidone; History of sensitivity to weight gain, hyperglycemia, or hyperlipidemia-G2 ziprasidone or aripiprazole; Repeated nonadherence to pharmacological treatment-G4 (taken from the Practice Guidelines for the Treatment of Patients with Bipolar Disorder, Second Edition from the American Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders Compendium, Copyright 2004).

FIGURE 1-1. Somatic Treatment of Schizophrenia. Also refer to Table 1-1 and the following: First episode-Group(G) 2; Persistent suicidal ideation or behavior-G3; Persistent hostility and aggressive behavior-G3; Tardive dyskinesia-G2 all group 2 drugs may not be equal in their lower or no tardive dyskinesia liability and G3; History of sensitivity to extrapyramidal side effects-G2 except higher doses of risperidone; History of sensitivity to prolactin elevation-G2 except risperidone; History of sensitivity to weight gain, hyperglycemia, or hyperlipidemia-G2 ziprasidone or aripiprazole; Repeated nonadherence to pharmacological treatment-G4 (taken from the Practice Guidelines for the Treatment of Patients with Bipolar Disorder, Second Edition from the American Psychiatric Association Practice Guidelines for the Treatment of Psychiatric Disorders Compendium, Copyright 2004).

and psychotic symptom resolution, clinicians consider long-term side effect profiles of the available treatment options with the goal of minimizing long-term side effect burden. Ziprasi-done and aripiprazole may be specifically indicated in patients who are intolerant of the side effects that can occur in greater frequency with some of the second-generation drugs, such as weight gain and alterations in glucose and lipid metabolism, as they do not produce these effects to any significant degree.

One can safely escalate the dose of second-generation antipsychotics more rapidly than is usual in outpatient settings to achieve target doses typically utilized for the treatment of schizophrenia. Once behavioral control is achieved, benzo-diazepines should be discontinued and the patient should be maintained on the atypical antipsychotic alone. The dose recommendations for second-generation antipsychotic drugs are summarized in Table 1-2.

The anti-aggressive characteristics of clozapine are well established in chronically psychotic patients; however cloza-pine initiation is contraindicated in the psychiatric emergency setting because of its serious potential side effects, including seizures and agranulocytosis.

On the rare occasion that a physician elects to use a firstgeneration antipsychotic during the first few days of treatment, "rapid neuroleptization" should be avoided as there is no evidence for increased efficacy and risk of side effects is greater at higher doses. If a low-potency agent is chosen, the recommendation is to begin with a low dose such as chlorpromazine, 50 mg twice a day, and to titrate slowly so that the difficulties associated with orthostatic hypotension can be reduced. If a high-potency agent such as haloperidol is chosen, the recommendation is also to begin a course of prophylactic antiparkin-sonism medication such as benztropine, 1 mg twice a day, to decrease the incidence of EPS side effects. The initial dose of antipsychotic should be titrated to between 5 and 10 haloperidol equivalents or 200 to 400 chlorpromazine equivalents. At this time, the only groups of patients in which the first-generation antipsychotics are clearly preferable are those who have a history of good response to these agents with minimal side effects.

After initiating treatment and titrating to a standard dose of antipsychotic, the clinician, patient, and family must wait for the antipsychotic to take effect. Because patients are acutely

■ TABLE 1-2. Recommended Dosages for Second-Generation Antipsychotic Agents

AVERAGE DOSE RANGE (mg/day)

AVERAGE

HALF-LIFE

STARTING DOSE

MAINTENANCE DOSE

ROUTES OF

(hr) (MEAN)

(TOTAL mg/day)

FIRST EPISODE

RECURRENT EPISODE

(mg/day)

ADMINISTRATION

Clozapine

10-105 (16)

25-50

150-300

400-600

400

Oral

Risperidone

3-24 (15)

1-2

2-4

3-6

3-6

Oral, depot

Olanzapine

20-70 (30)

5-10

10-20

15-30

10-20

Oral, IM

Quetiapine

4-10 (7)

50-100

300-600

500-800

400-800

Oral

Ziprasidone

4-10

40-80

80-120

120-200

120-160

Oral, IM

Zotepine

12-30 (15)

50-100

75-150

150-450

75-300

Oral

Amisulpride

8-20 (12)

50-100

50-300

400-800

400-800

Oral

Aripiprazole

(75-96)

10-15

10-30

15-30

15-30

Oral

Source: Adapted from McEvoy JP, Scheifler PL, Frances A (1999) The expert consensus guideline series: Treatment of schizophrenia. / Clin Psychiatr 60,1-80; Burns MJ (2001) The pharmacology and toxicology of atypical antipsychotic agents. / Clin Toxicol 39, 1-14; Worrel JA, Marken PA, Beckman SE, et al. (2000) Atypical antipsychotic agents: A critical review. Am J Health Syst Pharm 57, 238-255.

Source: Adapted from McEvoy JP, Scheifler PL, Frances A (1999) The expert consensus guideline series: Treatment of schizophrenia. / Clin Psychiatr 60,1-80; Burns MJ (2001) The pharmacology and toxicology of atypical antipsychotic agents. / Clin Toxicol 39, 1-14; Worrel JA, Marken PA, Beckman SE, et al. (2000) Atypical antipsychotic agents: A critical review. Am J Health Syst Pharm 57, 238-255.

ill, there is often a tremendous temptation and external pressure to increase the dose of the antipsychotic in the hope that the patient's condition will improve more rapidly. Despite this hope, there is little, if any, clinical evidence that a higher dose of antipsychotic is in any way advantageous; in fact, it will only increase the likelihood of side effects. During this difficult time it may be necessary to add sedating medications such as short-acting benzodiazepines (e.g., lorazepam) to help the patient maintain control until the antipsychotic has started to work.

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  • diana
    What drugs not suitable for titration against response?
    10 days ago

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