An Insomnia Algorithm

Noon, Rest from Work by Vincent van Gogh

Most sleep meds were tested on primary insomnia patients. Here’s a guide built for the secondary insomnia we typically see.

STUDY: Chen A et al, J Clin Psychopharmacol 2026

STUDY TYPE: Expert consensus algorithm

FUNDING: Independent

Background

The Harvard South Shore Psychopharmacology Algorithm Project reviewed the evidence for treating insomnia in psychiatric disorders and built a decision tree.

The Study

• A narrative review of controlled trials, meta-analyses, and prior Harvard algorithms for major depressive disorder, generalized anxiety disorder, PTSD, and bipolar mania.
• Authors synthesized findings into a six-node flowchart, prioritizing treatments by quality of evidence and tolerability.
• Primary insomnia, without a psychiatric diagnosis, was excluded.

Results

The algorithm begins with a biopsychosocial evaluation to identify the psychiatric driver of the insomnia. When more than one disorder is present, treat the one contributing most to the sleep problem first.

For major depressive disorder, eszopiclone has the strongest evidence base — at least seven studies — and improves both sleep and depression scores. Trazodone up to 100 mg is a reasonable second choice, though avoid it with fluoxetine or paroxetine due to a metabolite (m-CPP) that can cause anxiety and dysphoria. Benzodiazepines come last, given dependence risk and cognitive side effects. Zolpidem carries a new caution: a 2022 meta-analysis of over 340,000 patients found an 88% higher rate of suicide or suicide attempt with its use, though confounding by indication can’t be ruled out.

For generalized anxiety disorder, eszopiclone and zolpidem both have trial support. If an SSRI is causing the insomnia in GAD, consider switching to hydroxyzine or pregabalin, both of which treat anxiety and improve sleep.

For PTSD, prazosin is the standout choice. Ten placebo-controlled trials exist, seven positives. The effective dose is higher than many clinicians use: a mean of 16 mg at night and 5 mg in the morning for men, and 7 mg at night and 2 mg in the morning for women, after slow titration over a month.

For bipolar mania, a second-generation antipsychotic treats both the mania and the insomnia (Dr. Aiken’s tip: quetiapine has the best evidence to deepen sleep; lumateperone is also a good choice. However, for bipolar depression ramelteon is safer and has evidence to prevent bipolar depression). A short-term benzodiazepine can bridge the gap while the mood stabilizer takes effect. Avoid antidepressants.

For conditioned insomnia — the fear of sleeplessness that persists after the original cause is gone — cognitive behavioral therapy for insomnia (CBT-I) is the treatment of choice (consider the Sleep Coach app).

Practice Implications

1. Find more algorithms from the Harvard group here.