Insomnia and related mental health conditions: Essential neurobiological underpinnings towards reduced polypharmacy utilization rates.

Insomnia represents a significant public health burden, with a 10% prevalence in the general population. Reduced sleep affects social and working functioning, productivity, and patient's quality of life, leading to a total of $100 billion per year in direct and indirect healthcare costs. Primary insomnia is unrelated to any other mental or medical illness; secondary insomnia co-occurs with other underlying medical, iatrogenic, or mental conditions. Epidemiological studies found a 40-50% comorbidity prevalence between insomnia and psychiatric disorders, suggesting a high relevance of mental health in insomniacs. Sleep disturbances also worsen the outcomes of several psychiatric disorders, leading to more severe psychopathology and incomplete remission, plausibly contributing to treatment-resistant conditions. Insomnia and psychiatric disorder coexistence can lead to polypharmacy, namely, the concurrent use of two or more medications in the same patient, regardless of their purpose or rationale. Polypharmacy increases the risk of using unnecessary drugs, the likelihood of drug interactions and adverse events, and reduces the patient's compliance due to regimen complexity. The workup of insomnia must consider the patient's sleep habits and inquire about any medical and mental concurrent conditions that must be handled to allow insomnia to be remitted adequately. Monotherapy or limited polypharmacy should be preferred, especially in case of multiple comorbidities, promoting multipurpose molecules with sedative properties and with bedtime administration. Also, non-pharmacological interventions for insomnia, such as sleep hygiene, relaxation training and Cognitive Behavioral Therapy may be useful in secondary insomnia to confront behaviors and thoughts contributing to insomnia and help optimizing the pharmacotherapy. However, insomnia therapy should always be patient-tailored, considering drug indications, contraindications, and pharmacokinetics, besides insomnia phenotype, clinical picture, patient preferences, and side effect profile.

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations.

Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.