Best Augmenting Combos for Partial Response or Treatment Resistance

• Valproic acid (valproate, divalproex, divalproex ER)

• Other mood-stabilizing anticonvulsants (carbamazepine, oxcarbazepine, lamotrigine)

• Lithium

• Benzodiazepines

• Fluoxetine and other antidepressants may be effective augmenting agents to olanzapine for bipolar depression, psychotic depression, and for unipolar depression not responsive to antidepressants alone (e.g., olanzapine-fluoxetine combination)

Tests 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

• Patients with liver disease should have blood tests a few times a year

• 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 olanzapine should be discontinued at the first sign of decline of WBC in the absence of other causative factors

Olanzapine: 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

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

• 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