Before starting an atypical antipsychotic

✽ Weigh all patients and track BMI during treatment

• Get baseline personal and family history of diabetes, obesity, dyslipidemia, hypertension, and cardiovascular disease

✽ Get waist circumference (at umbilicus), blood pressure, fasting plasma glucose, and fasting lipid profile

• Determine if the patient is

• overweight (BMI 25.0–29.9)

• obese (BMI ≥30)

• has pre-diabetes (fasting plasma glucose 100–125 mg/dL)

• has diabetes (fasting plasma glucose >126 mg/dL)

• has hypertension (BP >140/90 mm Hg)

• has dyslipidemia (increased total cholesterol, LDL cholesterol, and triglycerides; decreased HDL cholesterol)

• Treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management

Monitoring after starting an atypical antipsychotic

✽ BMI monthly for 3 months, then quarterly

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

✽ Blood pressure, fasting plasma glucose, fasting lipids within 3 months and then annually, but earlier and more frequently for patients with diabetes or who have gained >5% of initial weight

• Treat or refer for treatment and consider switching to another atypical antipsychotic for patients who become overweight, obese, pre-diabetic, diabetic, hypertensive, or dyslipidemic while receiving an atypical antipsychotic

✽ Even in patients without known diabetes, be vigilant for the rare but life-threatening onset of diabetic ketoacidosis, which always requires immediate treatment, by monitoring for the rapid onset of polyuria, polydipsia, weight loss, nausea, vomiting, dehydration, rapid respiration, weakness and clouding of sensorium, even coma

• Liver function testing, electrocardiogram, general physical exam, and assessment of baseline cardiac status before starting treatment

• Liver tests may be necessary during treatment in patients who develop nausea, vomiting, or anorexia

✽ Electrocardiograms and cardiac evaluation to rule out myocarditis may be necessary during treatment in patients who develop shortness of breath or chest pain

Clozapine: side effects How Drug Causes Side Effects

• By blocking histamine 1 receptors in the brain, it can cause sedation and possibly weight gain

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

• By blocking muscarinic 1 receptors, it can cause dry mouth, constipation, and sedation, or even paralytic ileus

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

• Mechanism of weight gain and increased incidence of diabetes and dyslipidemia with atypical antipsychotics is unknown but insulin regulation may be impaired by blocking pancreatic M3 muscarinic receptors

Notable Side Effects

✽ Probably increases risk for diabetes and dyslipidemia

✽ Increased salivation (can be severe)

✽ Sweating

• Dizziness, sedation, headache, tachycardia, hypotension

• Nausea, constipation, dry mouth, weight gain

• Rare tardive dyskinesia (no reports have directly implicated clozapine in the development of tardive dyskinesia)