Personalizing antipsychotic therapy to improve functional outcomes and quality of life

The ideal antipsychotic

The ideal antipsychotic, said Professor Sigrid Casper, Vienna, Austria, should:

• Lead to resolution of symptoms — positive, negative, affective and cognitive
• Prevent relapse
• Be well tolerated with minimal adverse events to promote adherence
• Facilitate functioning, quality of life and, ultimately, recovery¹

The ideal antipsychotic should be effective and well tolerated by the patients

First-generation (typical) antipsychotics are D₂ receptor antagonists.² They are effective in treating the positive symptoms of schizophrenia, but also cause D₂ receptor antagonism-related extrapyramidal motor symptoms (EPS) — dystonia, akathisia and parkinsonian symptoms.³

Are the symptoms of schizophrenia or antipsychotic adverse events impairing functioning and quality of life? Or both?

Second-generation (atypical) antipsychotics include D₂ and serotonin (5-HT_2A) receptor antagonists and partial D₂ receptor agonists.² They are effective at treating positive, negative and affective symptoms,⁴ and to some extent, some improve cognitive symptoms,⁵ explained Professor Casper.

Atypical antipsychotics also cause D₂ receptor antagonism-related EPS, but these are mitigated by the additional 5-HT_2A receptor antagonism and, in the case of the partial D₂ agonists, by partial D₂ agonism.²

Selecting a suitable antipsychotic for each patient is a step towards more personalized treatment

Many new antipsychotics targeting a variety of receptors are in the pipeline and may promise to further increase efficacy and improve tolerability.

Understanding the relationship between the pharmacology of different antipsychotics and their clinical effects is a step towards more personalized treatment for schizophrenia through selecting a suitable antipsychotic for each patient, said Professor Casper.

Weighing up efficacy vs tolerability

Relapse prevention depends upon adherence to antipsychotic therapy

A comparative efficacy and tolerability meta-analysis of 15 antipsychotic drugs has shown that; all antipsychotics are effective at treating the symptoms of schizophrenia, and differences in efficacy between different antipsychotics are small.⁶ However, they differ substantially in their adverse event profiles.⁶

A key challenge for clinicians is to choose an antipsychotic medication for an individual patient that will effectively control their symptoms, while minimizing distressing or harmful adverse events,⁷ said Professor Casper — not only the EPS of the first-generation antipsychotics, but also the metabolic adverse events of second-generation antipsychotics.³

Adherence to antipsychotic therapy is best achieved by minimizing adverse events

All antipsychotics have adverse events, and patients are unlikely to take their medication if they have too many, said Professor Casper. It is necessary to assess how the adverse events, which vary in severity for different antipsychotics,⁶ interact with a patient’s life, including EPS, increased prolactin, sedation and weight gain.⁶

Do the adverse events of an antipsychotic interfere with the patient’s life?

Understanding the different efficacy and tolerability profiles, individual patient characteristics that might influence their pharmacological actions, and patient preference can inform and improve selection of antipsychotic therapy, leading to more personalized treatment for each individual patient, concluded Professor Casper.