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Chapter 4. Antipsychotic Drugs

DOI: 10.1176/appi.books.9781585624119.603204

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Observations in the late nineteenth century that aniline dyes had calming and sedating effects ultimately led to the development of the first phenothiazine, promethazine. In 1952, a related phenothiazine, chlorpromazine, was investigated as an antiautonomic drug to protect the body against its own excessive compensatory reactions during major surgery. It spread into psychiatry from the field of anesthesia after an initial clinical report by Delay et al. (1952) demonstrated the drug's favorable side-effect profile and its efficacy in treating acute psychosis. Endless subsequent double-blind studies have served chiefly to confirm the effects already obvious to the original French clinicians.

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Table Reference Number
Table 4–1. Antipsychotic drugs: names, formulations, and strengths
Table Reference Number
Table 4–2. Antipsychotic drug potency
Table Reference Number

Note. CNS = central nervous system; EPS = extrapyramidal symptoms; EtOH = ethanol; FDA = U.S. Food and Drug Administration; NMS = neuroleptic malignant syndrome.

Second-generation (dopamine-serotonin antagonist) antipsychotics: overview

Efficacy

Schizophrenia (FDA approved for all)

Treatment-resistant schizophrenia (clozapine)

Mania (FDA approved for olanzapine, quetiapine, and ziprasidone)

Bipolar depression (FDA approved for quetiapine)

Depression/anxiety/agitation (efficacy established but not FDA approved for these purposes)

Side effects

Weight gain

Gastrointestinal effects

Insulin resistance

Sedation

Akathisia

Orthostatic hypotension

Bradykinesia

Tachycardia

Dizziness

Triglycerides (except ziprasidone)

EPS, NMS (rare)

Agranulocytosis (clozapine) (rare)

Seizures (clozapine)

Safety in overdose

Seizures with clozapine in overdose. Respiratory depression in combination with other CNS depressants. QT interval changes. Lavage and vital sign support.

Dosage and administration

Clozapine: 12.5–25 mg; then increase dosage 25–50 mg per week, as needed and tolerated, to 300–600 mg/day

Risperidone: 0.5–1 mg bid to 3 mg bid by end of first week, as tolerated

Olanzapine: 2.5–5 mg hs; increase by 5 mg every week to 20 mg hs

Quetiapine: 25 mg bid; increase total daily dose by 50 mg, as needed and tolerated, to 300–600 mg/day

Ziprasidone: 20 mg qd or bid; increase by 20–40 mg per week, to a maximum dosage of 80 mg bid

Aripiprazole: 15 mg qd; increase up to 30 mg/day after 1 week

Full benefits in 4 weeks to 6 months

Discontinuation

Mild cholinergic rebound, faster relapse.

Taper as slowly as titrated up.

Drug interactions

Fluvoxamine (1A2 inhibitor): second-generation antipsychotic levels

EtOH: sedation and orthostasis

Antihypertensives: may orthostasis

Carbamazepine: serum levels of olanzapine; clozapine levels; hematological adverse events with clozapine

CNS depressants: sedation

Ciprofloxacin (Cipro) (potent 1A2 inhibitor): second-generation antipsychotic levels

Table Reference Number
Table 4–3. APA/ADA recommendations for screening patients who are taking second-generation antipsychotics
Table Reference Number
Table 4–4. Guidelines for clozapine monitoring
Table Reference Number

Note. CNS = central nervous system; ECG = electrocardiogram; EPS = extrapyramidal symptoms; FDA = U.S. Food and Drug Administration; NMS = neuroleptic malignant syndrome; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant.

aAgitation associated with psychosis: FDA-approved indication for intramuscular olanzapine only.

Typical (D2 antagonist) antipsychotics: overview

Efficacy

Schizophrenia (positive symptoms) (FDA-approved indication)

Tourette's disorder (pimozide; FDA-approved indication)

Mania (FDA-approved indication for chlorpromazine only)

Psychotic depression (with antidepressant)

Drug-induced psychosis

Agitation,a nausea, hiccups (not FDA approved for these purposes; off-label)

Side effects

EPS (more common in high-potency drugs)

NMS (rare)

Dry mouth, constipation, urinary retention, sedation, weight gain (more common in low-potency drugs)

Skin and eye complications

QT interval prolongation (thioridazine)

Dosage and administration

Individualize dosing.

50–150 mg chlorpromazine equivalents (see Table 4–2Table 4–2) to start, with maximum total daily dose of 300–600 mg chlorpromazine equivalents (e.g., 6–12 mg haloperidol).

Safety in overdose

CNS depression, hypotension, ECG changes, EPS. Manage with vital sign support, gastric lavage. Do not induce emesis secondary to aspiration risk.

Drug interactions

CNS depressants: sedation

Antacids: antipsychotic absorption

Carbamazepine: antipsychotic levels

SSRIs: antipsychotic levels

Nicotine: antipsychotic levels

Meperidine: sedation, hypotension

-Blockers: hypotension; may antipsychotic and -blocker levels

TCAs: may antipsychotic and TCA levels

Valproic acid: chlorpromazine may valproic acid levels

Table Reference Number
Table 4–5. Antiparkinsonian drugs: names, formulations and strengths, and dosage ranges
Table Reference Number
Table 4–6. Operational criteria for diagnosis of neuroleptic malignant syndrome

References

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