THERAPEUTICS

Brands

• INVEGA
• INVEGA SUSTENNA
• see index for additional brand names

Generic?

• No

Class

• Atypical antipsychotic (serotonin-dopamine antagonist; second-generation antipsychotics; also a mood stabilizer)

Commonly Prescribed for

• (bold for FDA approved)
• Schizophrenia
• Maintaining response in schizophrenia
• Schizoaffective disorder (INVEGA)
• Other psychotic disorders
• Bipolar disorder
• Behavioral disturbances in dementia
• Behavioral disturbances in children and adolescents
• Disorders associated with problems with impulse control

How the Drug Works

• Blocks dopamine 2 receptors, reducing positive symptoms of psychosis and stabilizing affective symptoms
• Blocks serotonin 2A receptors, causing enhancement of dopamine release in certain brain regions and thus reducing motor side effects and possibly improving cognitive and affective symptoms
• Alpha 2 antagonist properties may contribute to antidepressant actions

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
• Classically recommended to wait at least 4–6 weeks to determine efficacy of drug, but in practice some patients may require up to 16–20 weeks to show a good response, especially on cognitive symptoms

If It Works

• Most often reduces positive symptoms but does not eliminate them
• Can improve negative symptoms, as well as aggressive, cognitive, and affective symptoms in schizophrenia
• Most schizophrenia patients do not have a total remission of symptoms but rather a reduction of symptoms by about a third
• Perhaps 5–15% of schizophrenia 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 superresponders 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

If It Doesn’t Work

• Try one of the other atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, amisulpride, asenapine, iloperidone, lurasidone)
• If 2 or more antipsychotic monotherapies do not work, consider clozapine
• If no first-line atypical antipsychotic is effective, consider higher doses or augmentation with valproate or lamotrigine
• Some patients may require treatment with a conventional antipsychotic
• Consider noncompliance and switch to another antipsychotic with fewer side effects or to an antipsychotic that can be given by depot injection (a depot formulation of paliperidone is in development)
• 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)
• Other mood-stabilizing anticonvulsants (carbamazepine, oxcarbazepine, lamotrigine)
• Lithium
• Benzodiazepines

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 100–25 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
• 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, than 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
• 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 paliperidone should be discontinued at the first sign of decline of WBC in the absence of other causative factors