Can clomipramine (a tricyclic antidepressant) help treat major depressive disorder?

From the Guidelines

Clomipramine can be used to treat depression, but it is not the first-line treatment due to its side effects and the availability of safer alternatives, such as second-generation antidepressants. Clomipramine is a tricyclic antidepressant that works by increasing levels of serotonin and norepinephrine in the brain, which helps improve mood, sleep, appetite, and energy levels. The typical starting dose is 25 mg daily, gradually increasing to 100-250 mg daily, usually taken in divided doses or as a single bedtime dose to minimize daytime side effects. Treatment typically requires 2-4 weeks before significant improvement occurs, and should continue for at least 6-12 months after symptoms resolve to prevent relapse, as recommended by the American College of Physicians 1.

Key Considerations

• Common side effects include dry mouth, constipation, blurred vision, drowsiness, dizziness, and sexual dysfunction.
• Patients should be aware that abrupt discontinuation can cause withdrawal symptoms, so dosage should be tapered gradually under medical supervision.
• While effective for depression, clomipramine is particularly known for treating obsessive-compulsive disorder (OCD).
• Due to potential serious side effects including cardiac issues, regular monitoring by a healthcare provider is essential, especially during the initial treatment period.
• The American College of Physicians recommends that clinicians continue treatment for 4 to 9 months after a satisfactory response in patients with a first episode of major depressive disorder, and for patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 1.

Treatment Approach

• The goal of treatment is to improve symptoms, prevent relapse, and improve quality of life.
• Treatment should be individualized based on patient preferences, medical history, and response to treatment.
• Regular follow-up with a healthcare provider is essential to monitor treatment response, side effects, and adjust treatment as needed.
• According to the most recent guideline from the American College of Physicians, published in 2016, clinicians should select between either cognitive behavioral therapy or second-generation antidepressants to treat patients with major depressive disorder after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient 1.

From the Research

Clomipramine and Depression

• Clomipramine has been established as a treatment for depressive illness, particularly treatment-resistant depression 2.
• The drug has been shown to be effective in the management of depression, resistant depression, and obsessive compulsive disorder 3.
• Clomipramine is particularly well suited for the treatment of resistant depression, for which its efficacy may be enhanced by combination therapy with tryptophan and/or lithium 3.
• Clinical trials have demonstrated the drug's effectiveness in the treatment of depression, with significant improvements in symptoms 4, 5.

Dose-Effect Relationship

• A dose-effect study in patients with depression found a moderate and statistically significant relationship between depression rating and dose at all ratings after 1 to 6 weeks of treatment 6.
• The study found that early sustained response occurred more frequently with the two highest doses (125 and 200 mg/day) 6.
• Serum levels of clomipramine and desmethylclomipramine showed a weak correlation with depression ratings 6.

Adverse Effects

• The most common adverse effects of clomipramine are anticholinergic, with others including nausea, seizures, and sexual difficulties 4, 5.
• The incidence of seizures is dose-related, occurring in 0.48% of all patients receiving clomipramine less than or equal to 250 mg/day and 2.1% of patients receiving greater than or equal to 300 mg/day 2.
• Drop-outs attributable to adverse events increased with rising doses in a dose-effect study 6.