THERAPEUTICS

Brands

• Solian
• see index for additional brand names

Generic?

• No

Class

• A typical antipsychotic (benzamide; possibly a dopamine stabilizer and dopamine partial agonist)

Commonly Prescribed for

• (bold for FDA approved)
• Schizophrenia, acute and chronic (outside of U.S., especially Europe)
• Dysthymia

How the Drug Works

• Theoretically blocks presynaptic dopamine 2 receptors at low doses
• Theoretically blocks postsynaptic dopamine 2 receptors at higher doses
• May be a partial agonist at dopamine 2 receptors, which would theoretically reduce dopamine output when dopamine concentrations are high and increase dopamine output when dopamine concentrations are low
• Blocks dopamine 3 receptors, which may contribute to its clinical actions
• Unlike other atypical antipsychotics, amisulpride does not have potent actions at serotonin receptors

How Long Until It Works

• Psychotic symptoms can improve within 1 week, but it may take several weeks for full effect on behavior as well as on cognition and affective stabilization
• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients require up to 16–20 weeks to show a good response, especially on cognitive symptoms

If It Works

• Most often reduces positive symptoms in schizophrenia but does not eliminate them
• Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia
• Most schizophrenic patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third
• Perhaps 5–15% of schizophrenic patients can experience an overall improvement of greater than 50–60%, especially when receiving stable treatment for more than a year
• Such patients are considered super-responders or “awakeners” since they may be well enough to be employed, live independently, and sustain long-term relationships
• Continue treatment until reaching a plateau of improvement
• After reaching a satisfactory plateau, continue treatment for at least a year after first episode of psychosis
• For second and subsequent episodes of psychosis, treatment may need to be indefinite
• Even for first episodes of psychosis, it may be preferable to continue treatment indefinitely to avoid subsequent episodes

If It Doesn’t Work

• Try one of the other first-line atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone, asenapine, iloperidone, lurasidone)
• If two or more antipsychotic monotherapies do not work, consider clozapine
• Some patients may require treatment with a conventional antipsychotic
• If no atypical antipsychotic is effective, consider higher doses or augmentation with valproate or lamotrigine
• Consider noncompliance and switch to another antipsychotic with fewer side effects or to an antipsychotic that can be given by depot injection
• Consider initiating rehabilitation and psychotherapy
• Consider presence of concomitant drug abuse

Best Augmenting Combos for Partial Response or Treatment Resistance

• Valproic acid (valproate, divalproex, divalproex ER)
• Augmentation of amisulpride has not been systematically studied
• Other mood-stabilizing anticonvulsants (carbamazepine, oxcarbazepine, lamotrigine)
• Lithium
• Benzodiazepines

Tests

• Although risk of diabetes and dyslipidemia with amisulpride has not been systematically studied, monitoring as for all other atypical antipsychotics is suggested

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 waistline circumference (at umbilicus), blood pressure, fasting plasma glucose, and fasting lipid profile
• Determine if patient is
  • overweight (BMI 25.0–29.9)
  • obese (BMI ≥30)
  • has pre-diabetes (fasting plasma glucose 100–25 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% 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
• EKGs may be useful for selected patients (e.g., those with personal or family history of QTc prolongation; cardiac arrhythmia; recent myocardial infarction; uncompensated heart failure; or taking agents that prolong QTc interval such as pimozide, thioridazine, selected antiarrhythmics, moxifloxacin, sparfloxacin, etc.)
• Patients at risk for electrolyte disturbances (e.g., patients on diuretic therapy) should have baseline and periodic serum potassium and magnesium measurements
• 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 amisulpride should be discontinued at the first sign of decline of WBC in the absence of other causative factors