What are the recent advancements in psychopharmacology for treating mental health disorders?

From the Guidelines

Recent advancements in psychopharmacology have significantly expanded treatment options for mental health disorders, with a focus on improving morbidity, mortality, and quality of life outcomes.

Key Developments

• Novel antidepressants like esketamine (Spravato), administered as a nasal spray at 56-84mg twice weekly for 4 weeks then weekly or biweekly, offer rapid relief for treatment-resistant depression 1.
• Antipsychotic polypharmacy, such as combining aripiprazole with clozapine, may be effective in reducing treatment side effects or residual symptoms in patients with schizophrenia, as suggested by recent studies 1.
• New atypical antipsychotics such as lumateperone (Caplyta, 42mg daily) demonstrate improved metabolic profiles for schizophrenia and bipolar disorder.
• Extended-release formulations like paliperidone palmitate (Invega Hafyera, administered once every six months) improve medication adherence.
• Selective GABA modulators including brexanolone (Zulresso) for postpartum depression and zuranolone for major depression provide targeted treatment with fewer side effects.

Treatment Considerations

• Antipsychotic monotherapy should be strived for, with clozapine tried at the latest if two monotherapy trials with other antipsychotics have failed and no absolute contraindications exist 1.
• Antipsychotic polypharmacy may be considered in certain situations, such as for clozapine-resistant patients or in patients with treatment-resistant schizophrenia 1.
• Digital therapeutics that combine medication with software applications are emerging, while pharmacogenetic testing helps identify optimal medications based on individual genetic profiles, reducing trial-and-error approaches.

Evidence-Based Recommendations

• The most recent guidelines, such as the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guideline, recommend a range of psychotherapies for treatment of depression, including ketamine and esketamine for patients who have not responded to other treatments 1.
• The use of antipsychotic polypharmacy should be considered on a case-by-case basis, taking into account the individual patient's needs and circumstances, and with careful monitoring of side effects and treatment outcomes 1.

From the FDA Drug Label

SPRAVATO is a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist indicated for the treatment of: Treatment-resistant depression (TRD) in adults, as monotherapy or in conjunction with an oral antidepressant Depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior in conjunction with an oral antidepressant.

The most recent advancements in psychopharmacology for treating mental health disorders include the use of esketamine (IN), specifically SPRAVATO, for the treatment of treatment-resistant depression (TRD) and depressive symptoms in adults with major depressive disorder (MDD) with acute suicidal ideation or behavior.

• Key benefits: SPRAVATO has been shown to be effective in reducing depressive symptoms in adults with TRD and MDD with acute suicidal ideation or behavior.
• Administration: SPRAVATO is administered intranasally under the supervision of a healthcare provider, with a recommended dosage and administration instructions outlined in the full prescribing information 2.
• Important warnings and precautions: Increases in blood pressure, cognitive impairment, impaired ability to drive and operate machinery, and embryo-fetal toxicity are potential risks associated with SPRAVATO use 2.

From the Research

Recent Advancements in Psychopharmacology

The field of psychopharmacology has seen significant advancements in recent years, particularly in the treatment of mental health disorders. Some of the key developments include:

• The use of atypical antipsychotics in the treatment of depressive syndromes, as discussed in the study by 3. This study found that atypical antipsychotics, such as amisulpride, olanzapine, and clozapine, have shown antidepressant effects, particularly in association with selective serotonin reuptake inhibitors (SSRIs).
• The introduction of esketamine, a non-monoaminergic-based drug, which has been approved for the treatment of treatment-resistant depression (TRD) 4, 5. Esketamine has been shown to have rapid antidepressant effects, with a significant reduction in depressive symptoms and suicidal ideation.

Treatment-Resistant Depression

Treatment-resistant depression (TRD) is a significant challenge in psychiatry, with limited treatment options available. Recent studies have investigated the use of esketamine in TRD, with promising results:

• A review of clinical evidence found that esketamine is effective in reducing depressive symptoms in patients with TRD, with a rapid onset of action 4.
• Case presentations have demonstrated the effectiveness of intranasal esketamine in patients with TRD, including those with psychiatric emergencies such as suicidal ideation 6.
• A review of the current literature found that atypical antipsychotics, such as aripiprazole, olanzapine, and risperidone, may be effective as augmentation agents in the treatment of unipolar, nonpsychotic depression 7.

Future Directions

While these advancements are promising, further research is needed to fully understand the efficacy and safety of these treatments:

• More studies are needed to assess the long-term efficacy and safety of esketamine in TRD 4.
• Novel directions for research have been identified, including the use of esketamine in patients with TRD and substance use disorders, geriatric or bipolar depression, or major depression with psychotic features 4.
• Further investigation is needed to determine the optimal duration and frequency of treatment with esketamine, as well as its potential addictive potential 5.