THERAPEUTICS

Brands

• Thorazine
• see index for additional brand names

Generic?

• Yes

Class

• Conventional antipsychotic (neuroleptic, phenothiazine, dopamine 2 antagonist, antiemetic)

Commonly Prescribed For

• (bold for FDA approved)
• Schizophrenia
• Nausea, vomiting
• Restlessness and apprehension before surgery
• Acute intermittent porphyria
• Manifestations of manic type of manic-depressive illness
• Tetanus (adjunct)
• Intractable hiccups
• Combativeness and/or explosive hyperexcitable behavior (in children)
• Hyperactive children who show excessive motor activity with accompanying conduct disorders consisting of some or all of the following symptoms: impulsivity, difficulty sustaining attention, aggressivity, mood lability, and poor frustration tolerance
• Psychosis
• Bipolar disorder

How The Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and improving other behaviors
• Combination of dopamine D2, histamine H1, and cholinergic M1 blockade in the vomiting center may reduce nausea and vomiting

How Long Until It Works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior
• Actions on nausea and vomiting are immediate

If It Works

• Most often reduces positive symptoms in schizophrenia but does not eliminate them
• Most schizophrenic patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third
• Continue treatment in schizophrenia until reaching a plateau of improvement
• After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis in schizophrenia
• For second and subsequent episodes of psychosis in schizophrenia, treatment may need to be indefinite
• Reduces symptoms of acute psychotic mania but not proven as a mood stabilizer or as an effective maintenance treatment in bipolar disorder
• After reducing acute psychotic symptoms in mania, switch to a mood stabilizer and/or an atypical antipsychotic for mood stabilization and maintenance

If It Doesn’t Work

• Consider trying one of the first-line atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride)
• Consider trying another conventional antipsychotic
• If 2 or more antipsychotic monotherapies do not work, consider clozapine

Best Augmenting Combos for Partial Response or Treatment-Resistance

• Augmentation of conventional antipsychotics has not been systematically studied
• Addition of a mood stabilizing anticonvulsant such as valproate, carbamazepine, or lamotrigine may be helpful in both schizophrenia and bipolar mania
• Augmentation with lithium in bipolar mania may be helpful
• Addition of a benzodiazepine, especially short-term for agitation

Tests

• Since conventional antipsychotics are frequently associated with weight gain, before starting treatment, weigh all patients and determine if the patient is already overweight (BMI 25.0–29.9) or obese (BMI ≥30)
• Before giving a drug that can cause weight gain to an overweight or obese patient, consider determining whether the patient already has pre-diabetes (fasting plasma glucose 100–125 mg/dL), diabetes (fasting plasma glucose >126 mg/dL), or dyslipidemia (increased total cholesterol, LDL cholesterol and triglycerides; decreased HDL cholesterol), and treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management
• Monitor weight and BMI during treatment
• While giving a drug to a patient who has gained >5% of initial weight, consider evaluating for the presence of pre-diabetes, diabetes, or dyslipidemia, or consider switching to a different antipsychotic
• Should check blood pressure in the elderly before starting and for the first few weeks of treatment
• Monitoring elevated prolactin levels of dubious clinical benefit
• Phenothiazines may cause false positive phenylketonuria results