Pharmacotherapeutic strategies for the treatment of the most frequent psychiatric comorbidities in PTSD

INTRODUCTION: Posttraumatic stress disorder (PTSD) is trauma- and stressor-related disorder frequently associated with somatic and psychiatric comorbidities. The most frequent psychiatric comorbidities are major depressive disorder (MDD), sleep disturbances, alcohol use disorders (AUD) and psychoses. The lack of clinical improvement is frequent in PTSD, and presence of comorbidities complicates PTSD treatment. AREAS COVERED: This narrative review covered pharmacotherapy of common psychiatric comorbidities in PTSD (MDD, psychosis, sleep disturbances, especially obstructive sleep apnea (OSA) and insomnia and AUD. We searched for novel data in reviews, randomized clinical trials, open labeled studies in English language through June 2026, identified using PubMed/MEDLINE/Web of Sciences/Google Scholar and clinical practice guidelines from the American Psychological Association for the Treatment of PTSD in adults (2025), and the US Department of Veterans Affairs and Department of Defense from 2023. We discussed available evidence related to pharmacotherapy of PTSD with comorbidities. EXPERT OPINION: The vast majority of PTSD patients have at least one psychiatric comorbidity. Pharmacological treatment represents a challenge, given that pharmacological agents used to treat PTSD mostly do not affect symptoms of other comorbid disorders. Therefore, the choice of medications is highly individual, depending on the clinical presentation, tolerability issues, physical comorbidities, and patient preference.