Pharmacological interventions for insomnia dysfunction in adults

A meta-analysis published in 2022 by Franco de Crescenzo and colleagues

suggested poor efficacy of pharmacotherapeutics in the treatment of insomnia disorder, which sits contrary to the outcomes of earlier meta-analyses. Despite such striking findings from transparent and rigorous methodology, there are multiple clinical scenarios and nuances in the pharmacotherapeutic treatment of sleep disorders that should also be considered.

At a basic level, there can be a logically precarious assumption that patients’ responses to a given intervention are homogeneous, yet insomnia is phenomenologically diverse, with phenotypes that might require different treatment approaches. For example, patients classified according to the short sleep phenotype, a severe phenotype characterised by insomnia with objective short sleep duration, respond poorly to cognitive behavioural therapy (CBT) for insomnia, which is the gold standard non-pharmacological therapeutic that is highly effective for many patients with insomnia who do not share this specific phenotype. However, trials comparing trazadone and CBT for insomnia in objective short sleepers concluded that only trazadone, and not CBT for insomnia, was effective at increasing total sleep time in this population.

Insomnia has consistently high rates of co-occurrence among medical and psychiatric disorders. Although the meta-analysis used secondary insomnia as an exclusion criterion, the third edition of the International Classification of Sleep Disorders and the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders no longer recognise secondary insomnia, instead classifying all cases, irrespective of comorbidity, as insomnia disorder. This distinction is clinically important because comorbid insomnia often necessitates pharmacological interventions, due to the poor efficacy of non-pharmacological alternatives. Many clinicians might interpret such findings as universal superiority of CBT for insomnia over pharmacotherapy; however, adherence to CBT for insomnia activities (eg, maintaining strict waking times) relies on intact self-efficacy and motivation, which is often not possible for people with psychiatric disorders such as depressive disorders and substance use disorders. Patients with insomnia who rate low in measures of self-efficacy and high in perceptions of boredom or irritation from CBT for insomnia report worse outcomes than patients who rate high in measures of self-efficacy and low in perceptions of boredom or irritation from CBT for insomnia.

Drop-out rates in CBT for insomnia trials for people with major depressive disorder have been as high as 64%,

and 50% of patients with post-traumatic stress disorder-associated insomnia still exhibited symptoms following a standardised course of CBT for insomnia.

Furthermore, in a study published in 2022

of patients with opioid use disorder undergoing medically supervised withdrawal (published after the meta-analysis was conducted), the dual orexin receptor antagonist suvorexant showed large improvements in subjective total sleep times (76·6% increase), objective total sleep times, and opioid cravings.

Indeed, de Crescenzo and colleagues acknowledge the challenges associated with prescribing opioids in combination with hypnotic agents in their Discussion,

and such interventions could offer viable alternatives in this population.