If It Doesn’t Work

• Consider trying one of the first-line atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, amisulpride, asenapine, iloperidone, lurasidone)

• 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

✽ Consider monitoring fasting triglycerides monthly for several months in patients at high risk for metabolic complications and when initiating or switching antipsychotics

✽ 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

• Patients with low white blood cell count (WBC) or history of drug-induced leucopenia/neutropenia should have complete blood count (CBC) monitored frequently during the first few months and zuclopenthixol should be discontinued at the first sign of decline of WBC in the absence of other causative factors

Zuclopenthixol: side effects How Drug Causes Side Effects

• By blocking dopamine 2 receptors in the striatum, it can cause motor side effects

• By blocking dopamine 2 receptors in the pituitary, it can cause elevations in prolactin

• By blocking dopamine 2 receptors excessively in the mesocortical and mesolimbic dopamine pathways, especially at high doses, it can cause worsening of negative and cognitive symptoms (neuroleptic-induced deficit syndrome)

• Anticholinergic actions may cause sedation, blurred vision, constipation, dry mouth

• Antihistaminic actions may cause sedation, weight gain

• By blocking alpha 1 adrenergic receptors, it can cause dizziness, sedation, and hypotension

• Mechanism of weight gain and any possible increased incidence of diabetes or dyslipidemia with conventional antipsychotics is unknown

Notable Side Effects

✽ Extrapyramidal symptoms

✽ Tardive dyskinesia (risk increases with duration of treatment and with dose)

✽ Priapism

✽ Galactorrhea, amenorrhea

• Rare lens opacity

• Sedation, dizziness

• Dry mouth, constipation, vision problems

• Hypotension

• Weight gain

Life-Threatening or Dangerous Side Effects

• Rare neuroleptic malignant syndrome

• Rare neutropenia

• Rare respiratory depression

• Rare agranulocytosis

• Rare seizures

• Increased risk of death and cerebrovascular events in elderly patients with dementia-related psychosis

Weight Gain

• Many experience and/or can be significant in amount

• Some people may lose weight

Sedation

• Many experience and/or can be significant in amount

• Acetate formulation may be associated with an initial sedative response

What to Do About Side Effects

• Wait

• Wait

• Wait

• For motor symptoms, add an anticholinergic agent

• Reduce the dose

• For sedation, take at night

• Switch to an atypical antipsychotic

• Weight loss, exercise programs, and medical management for high BMIs, diabetes dyslipidemia

Best Augmenting Agents for Side Effects

• Benztropine or trihexyphenidyl for motor side effects

• Sometimes amantadine can be helpful for motor side effects

• Benzodiazepines may be helpful for akathisia

• Many side effects cannot be improved with an augmenting agent

ZUCLOPENTHIXOL: DOSING AND USE

Usual Dosage Range

• Oral 20–60 mg/day

• Acetate 50–150 mg every 2–3 days

• Decanoate 150–300 mg every 2–4 weeks

Dosage Forms

• Tablet 10 mg, 25 mg, 40 mg

• Acetate 50 mg/mL (equivalent to zuclopenthixol 45.25 mg/mL), 100 mg/2 mL (equivalent to zuclopenthixol 45.25 mg/mL)

• Decanoate 200 mg/mL (equivalent to zuclopenthixol 144.4 mg/mL), 500 mg/mL (equivalent to zuclopenthixol 361.1 mg/mL)

How to Dose

• Oral: initial 10–15 mg/day in divided doses; can increase by 10–20 mg/day every 2–3 days; maintenance dose can be administered as a single nighttime dose; maximum dose generally 100 mg/day

• Injection should be administered intramuscularly in the gluteal region in the morning

• Acetate generally should be administered every 2–3 days; some patients may require a second dose 24–48 hours after the first injection; duration of treatment should not exceed 2 weeks; maximum cumulative dosage should not exceed 400 mg; maximum number of injections should not exceed 4

• Decanoate: initial dose 100 mg; after 1–4 weeks administer a second injection of 100–200 mg; maintenance treatment is generally 100–600 mg every 1–4 weeks