Trade name: Anafranil, Anafranil SR
Pharmacological Properties
Clomipramine is one of the key representatives of tricyclic antidepressants, alongside amitriptyline and imipramine. In terms of its pharmacological profile, it occupies an intermediate position between the two: amitriptyline primarily exerts a sedative effect, imipramine — a stimulating one, while clomipramine combines both effects in a balanced manner.
The mechanism of action of clomipramine involves strong modulation of the serotonergic system. In terms of its action on cholinergic, adrenergic, and histaminergic receptors, it is most similar to imipramine. This makes it particularly effective in treating depression with endogenous features, especially when there are prominent circadian mood variations and autonomic dysfunction. It has also proven effective in patients resistant to other tricyclic antidepressants, including amitriptyline and imipramine.
Clinical Use
Clomipramine holds a special place in the treatment of obsessive-compulsive disorder (OCD). It is considered one of the most effective antidepressants for managing obsessions — whether related to endogenous conditions or neurotic disorders. It may also be used in cases of severe anxiety, panic attacks, and phobic disorders, particularly when other anxiolytics have failed.
Although tricyclic antidepressants in general can enhance sympathetic activity, clinical observations indicate that clomipramine (similar to amitriptyline and imipramine) can effectively alleviate autonomic symptoms, including those related to anxiety and panic.
Forms and Dosing Schedules
Clomipramine is available in both oral and intravenous forms. In OCD treatment, the oral route is typically preferred. IV therapy usually begins with 25 mg dissolved in 250–300 ml of saline or 5% glucose. The infusion is administered once daily, increasing the dose by 25 mg each day until the therapeutic level — typically 150 mg — is reached. Exceeding this dose in IV form is not recommended.
The antidepressant effect develops gradually, while the anxiolytic effect may appear after just a few sessions. Once the target dose is achieved, the infusions are continued for another 4–5 days. If clinical improvement is observed, treatment is extended by 3–5 days and then transitioned to oral form, following a gradual adjustment (e.g., 25 mg IV = 50 mg oral).
Oral therapy starts with low doses (12.5–25 mg), which are increased every 3–4 days. Once a dose of 75 mg is reached, a pause of 10–14 days is often made to assess response. If no improvement is observed, the dose can be increased to the therapeutic range (100–150 mg, up to 250–300 mg in some cases).
The duration of treatment depends on the condition. For depression, one month of stable remission may be sufficient. In OCD, treatment needs to be significantly longer — early discontinuation often leads to relapse and withdrawal symptoms.
Side Effects and Management
Clomipramine’s side effect profile is similar to that of other tricyclic antidepressants and includes orthostatic hypotension, dizziness, a sensation of unsteadiness (the “rocking” effect), constipation, nausea, muscle twitching, and increased appetite. Increased appetite is usually manageable and rarely results in significant weight gain. After IV administration, the patient should remain in a lying position for at least one hour.
If side effects are numerous, severe, and persistent, it is advisable to consider switching the medication. In practice, early-onset severe side effects tend to persist and are often not accompanied by significant clinical improvement.
There may also be a phenomenon of diminishing efficacy despite a stable dose. This may be due to “slipping out” of the individual therapeutic window, often caused by dose escalation that is too rapid. If effectiveness decreases and side effects increase, it is advisable to return to the previously effective dose.
Conclusion
Clomipramine remains one of the most well-studied and reliable options for the treatment of endogenous depression and obsessive-compulsive disorder. Its therapeutic potential is especially significant in cases resistant to other antidepressants. At the Plexus Center for Psychiatry and Psychotherapy in Warsaw, we tailor antidepressant therapy individually — based on the patient’s clinical profile, tolerability, and treatment response. If you are struggling with persistent anxiety, obsessive thoughts, or treatment-resistant depression — we are here to help. We offer consultations in Polish and Russian, both in-person in Warsaw and online.