What is the recommended approach to initiating antipsychotic medication, including the choice of first-line treatment and management of potential side effects?

From the Guidelines

The recommended approach to initiating antipsychotic medication involves starting with a second-generation (atypical) antipsychotic as first-line treatment, with a comprehensive treatment plan that includes evidence-based nonpharmacological and pharmacological treatments, as recommended by the American Psychiatric Association (APA) 1.

Mechanism of Action

Antipsychotic medications work by modulating neurotransmitter systems in the brain, primarily dopamine and serotonin. Second-generation antipsychotics, such as risperidone, olanzapine, quetiapine, and aripiprazole, have a lower risk of extrapyramidal symptoms and tardive dyskinesia compared to first-generation antipsychotics. The APA recommends that patients with schizophrenia be treated with an antipsychotic medication and monitored for effectiveness and side effects 1.

Choice of First-Line Treatment

The choice of first-line treatment should be based on the individual patient's needs and preferences, as well as the potential side effects of the medication. For example, risperidone might start at 1-2mg daily, olanzapine at 5-10mg daily, quetiapine at 25-50mg twice daily, or aripiprazole at 5-10mg daily. Regular monitoring is essential, with follow-up within 1-2 weeks of initiation and then every 2-4 weeks during dose adjustment.

Management of Potential Side Effects

To manage side effects, monitor for:

• Extrapyramidal symptoms (tremor, rigidity) which can be treated with anticholinergics like benztropine (1-2mg) if needed
• Weight gain and metabolic effects require baseline and regular monitoring of weight, blood glucose, and lipids
• Hyperprolactinemia may occur with some antipsychotics, potentially causing sexual dysfunction or menstrual irregularities
• QTc prolongation necessitates baseline and follow-up ECGs, especially with ziprasidone or high-dose quetiapine The APA suggests that patients who have acute dystonia associated with antipsychotic therapy be treated with an anticholinergic medication, and that patients who have parkinsonism or akathisia associated with antipsychotic therapy be treated with a variety of options, including lowering the dosage of the antipsychotic medication, switching to another antipsychotic medication, or treating with an anticholinergic medication 1.

Psychosocial Intervention

In addition to pharmacological treatment, psychosocial interventions are also essential for patients with schizophrenia. The APA recommends that patients with schizophrenia who are experiencing a first episode of psychosis be treated in a coordinated specialty care program, and that patients with schizophrenia be treated with cognitive-behavioral therapy for psychosis (CBTp), psychoeducation, supported employment services, and assertive community treatment if necessary 1. The overall goal of treatment is to enhance the treatment of schizophrenia, thereby reducing the mortality, morbidity, and significant psychosocial and health consequences of this important psychiatric condition, as recommended by the APA 1.

From the FDA Drug Label

Chronic antipsychotic treatment should generally be reserved for patients who suffer from a chronic illness that (1) is known to respond to antipsychotic drugs and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

The recommended approach to initiating antipsychotic medication includes:

• Reserving chronic treatment for patients with a chronic illness known to respond to antipsychotic drugs, and for whom alternative treatments are not available or appropriate.
• Using the smallest dose and shortest duration of treatment to produce a satisfactory clinical response.
• Periodically reassessing the need for continued treatment.
• Monitoring for side effects, such as metabolic changes, including hyperglycemia, dyslipidemia, and weight gain, as well as other potential side effects like orthostatic hypotension, somnolence, and leukopenia/neutropenia. Key considerations for managing potential side effects include:
• Regular monitoring of glucose control, blood pressure, and other metabolic parameters.
• Careful management of patients with risk factors for diabetes, cardiovascular disease, or other conditions that may be exacerbated by antipsychotic treatment.
• Prompt treatment of any symptoms or signs of infection, and careful monitoring of patients with neutropenia. It is essential to carefully evaluate the risks and benefits of antipsychotic treatment for each patient and to individualize treatment approaches based on specific patient needs and circumstances 2, 3, 3.

From the Research

Mechanism of Action of Antipsychotic Medications

• Antipsychotic medications are the mainstay in the pharmacologic treatment of schizophrenia, characterized by positive, negative, cognitive, disorganization, and mood symptoms 4.
• The efficacy of antipsychotics for positive symptoms and disorganization suggests no consistent differences among available antipsychotics, with the exception of clozapine's superior efficacy for treatment-resistant schizophrenia 4.
• The ability of antipsychotics to produce a potent antipsychotic effect without extrapyramidal side effects (EPS) and need for concomitant anticholinergic therapy yields multiple therapeutic benefits 4.

Choice of First-Line Treatment

• The choice of antipsychotic medication should be based on individual preference, prior treatment response and side effect experience, medical history and risk factors, and adherence history, with side effect profile a major determinant of antipsychotic choice 4.
• Second-generation antipsychotics (SGAs) have generally been believed to be associated with a lower risk of EPS but a higher risk of metabolic adverse effects than first-generation agents (FGAs) 4.
• However, the substantial variation in side effects among agents within both classes indicates that it is not clinically useful to make a categorical distinction between FGAs and SGAs 4.

Management of Potential Side Effects

• EPS and anticholinergic effects can exacerbate negative, depressive, and cognitive symptoms 4.
• The use of benzodiazepines differs between inpatients and outpatients, with inpatients prescribed benzodiazepines more often and in higher doses than outpatients 5.
• Inpatients receive higher doses of antipsychotics than outpatients, and the treatment setting needs to be taken into consideration in treatment recommendations for schizophrenia spectrum disorders 5.

Dosing Regimens

• Once-daily dosing of risperidone and olanzapine demonstrates significantly lower mean daily doses and lower rates of hospitalization for exacerbation of schizophrenia, sleepiness, and orthostatic faintness compared to twice-daily dosing 6.
• Effectiveness and efficacy outcomes between once- and twice-daily dosing for risperidone and olanzapine were not significantly different, but once-daily dosing is advisable due to the lower mean dose and better side effect profile 6.

Prescribing Patterns

• Guidelines for antipsychotic use in first-episode psychosis recommend that medication be chosen initially on the basis of side effect profile with doses at the lower end of the range 7.
• Second-generation antipsychotic prescribing predominates, but guidelines are often overlooked when choosing olanzapine notwithstanding lower initial dosages 7.
• Increasing dose requirements over the first month of engagement with an early intervention in psychosis (EIP) service was associated with poorer global functioning at baseline, greater positive symptoms at baseline, and the inpatient treatment setting 7.