Recent Advances in Psychopharmacology: From Bench to Bedside Novel Trends in Schizophrenia.

Research in the field of psychopharmacology is ongoing to develop novel compounds which can revolutionize the treatment of psychiatric disorders. The concept of bench-to-bedside is a tedious process, transforming the initial research performed in the laboratories into novel treatment options. Schizophrenia (SCZ) is a chronic psychiatric illness with significant morbidity and mortality. SCZ not only presents with psychotic symptoms including hallucinations and delusions but also with negative and cognitive symptoms. The negative symptoms include the diminished ability to express emotions, loss of pleasure, and motivation with minimal social interactions. Conventional antipsychotics primarily target positive symptoms with minimal therapeutic benefits for negative and cognitive symptoms along with metabolic side effects. Researchers have explored novel targets to develop new compounds to overcome the above limitations. The glutamatergic system has provided new hope in treating schizophrenia by targeting negative and cognitive symptoms. Other receptor modulators, including serotonergic, phosphodiesterase, trans-amine-associated receptors, etc., are novel targets for developing new compounds. Future research is required in this field to explore novel compounds and establish their efficacy and safety for the treatment of schizophrenia. Last but not least, pharmacogenomics has effectively utilized genetic information to develop novel compounds by minimizing the risk of failure of the clinical trials and enhancing efficacy and safety.

Ketamine for depression clinical issues.

Major depressive disorder (MDD) is a debilitating illness with significant morbidity and mortality, leading to attempted and completed suicides. It affects interpersonal relationships and also contributes to decreased productivity, causing financial burden to individuals and society. Patients often fail to respond to various antidepressant medication trials resulting in treatment-resistant depression (TRD). Current antidepressant medications work by modulating the monoaminergic systems and takes several weeks to establish a clinical response. Ketamine has been used extensively as an anesthetic agent since the 1970s, and more recent research has shown its rapid and robust effectiveness in TRD the subject of this review. Ketamine is a racemic mixture comprised of two enantiomers (R)-ketamine and (S)-ketamine and acts as an NMDA receptor antagonist. Most research studies have explored its antidepressant and antisuicidal effects by using it as an intravenous infusion or via the intranasal route due to increased bioavailability. Recently an intranasal esketamine spray was approved by the United States Food and Drug Administration (FDA) for TRD as an adjunct to standard antidepressant treatment in a supervised setting. Regarding its safety profile, multiple research studies have established the short-term safety and efficacy of ketamine in TRD. The cardiorespiratory and neuropsychiatric adverse events observed in these studies were mostly transient. However, ketamine is a scheduled agent with abuse potential, making its long-term use challenging and mandating further research.

Longer-term open-label study of adjunctive riluzole in treatment-resistant depression.

BACKGROUND: While riluzole has been investigated for the treatment of depression, little is known about its longer-term efficacy and optimal treatment duration in treatment-resistant depression (TRD). The objective of this study is to characterize the longer-term outcome of adjunctive riluzole therapy for TRD in an open-label extension of an 8-week acute treatment trial. METHODS: The data from 66 patients with TRD who received adjunctive riluzole in a 12-week open-label extension phase were analyzed. Response rates (⩾50% reduction in the Mongomery-Asberg Depression Rating Scale [MADRS] score), relapse rates (a MADRS score of ⩾22 in patients who had previously achieved response), and adverse events were examined in patients who had achieved response at the end of the acute phase and those who had not. RESULTS: Among acute phase responders, the maintained response rate was 66.7% (8/12) and the relapse rate was 8.3% (1/12). In acute phase non-responders, the response rate was 24.1% (13/54). The most commonly reported adverse event was fatigue (9.1%). Three cases were considered serious adverse events; vomiting (n = 1), shortness of breath (n = 1), and aborted suicide attempt (n = 1). LIMITATIONS: This longer-term study was open-label and uncontrolled. The sample size was relatively small. CONCLUSIONS: Longer-term adjunctive riluzole appears relatively well tolerated and beneficial for maintaining previous response. Additionally, approximately one fourth of patients who did not respond to 8-week antidepressant treatment might respond if treated with riluzole for 12 weeks. Those findings warrant further investigation because adjunctive riluzole could represent an option for treatment of depression when standard antidepressants have failed.

Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression.

BACKGROUND: Preliminary evidence suggests intravenous ketamine has rapid effects on suicidal cognition, making it an attractive candidate for depressed patients at imminent risk of suicide. In the first randomized controlled trial of ketamine using an anesthetic control condition, we tested ketamine's acute effects on explicit suicidal cognition and a performance-based index of implicit suicidal cognition (Implicit Association Test; IAT) previously linked to suicidal behavior. METHOD: Symptomatic patients with treatment-resistant unipolar major depression (inadequate response to ≥3 antidepressants) were assessed using a composite index of explicit suicidal ideation (Beck Scale for Suicidal Ideation, Montgomery-Asberg Rating Scale suicide item, Quick Inventory of Depressive Symptoms suicide item) and the IAT to assess suicidality implicitly. Measures were taken at baseline and 24 hr following a single subanesthetic dose of ketamine (n = 36) or midazolam (n = 21), a psychoactive placebo agent selected for its similar, rapid anesthetic effects. Twenty four hours postinfusion, explicit suicidal cognition was significantly reduced in the ketamine but not the midazolam group. RESULTS: Fifty three percent of ketamine-treated patients scored zero on all three explicit suicide measures at 24 hr, compared with 24% of the midazolam group (χ(2) = 4.6; P = .03). Implicit associations between self- and escape-related words were reduced following ketamine (P = .01; d = .58) but not midazolam (P = .68; d = .09). Ketamine-specific decreases in explicit suicidal cognition were largest in patients with elevated suicidal cognition at baseline, and were mediated by decreases in nonsuicide-related depressive symptoms. CONCLUSIONS: Intravenous ketamine produces rapid reductions in suicidal cognition over and above active placebo. Further study is warranted to test ketamine's antisuicidal effects in higher-risk samples.