Is clomipramine a tricyclic antidepressant? Understanding its classification and use

October 9, 2025 •

4 min read

Yes, clomipramine is a tricyclic antidepressant (TCA). Specifically, it is a dibenzazepine-derived TCA, distinct from newer classes of medications like SSRIs, and was the first drug approved by the FDA for the treatment of obsessive-compulsive disorder (OCD).

Quick Summary

Clomipramine, a tricyclic antidepressant, is primarily utilized for treating obsessive-compulsive disorder. It works by increasing levels of serotonin and norepinephrine in the brain, though it has a more significant side effect profile than selective serotonin reuptake inhibitors (SSRIs).

Key Points

TCA Classification: Clomipramine is a tricyclic antidepressant (TCA) with a distinct three-ring chemical structure.
Potent Serotonergic Action: Its primary mechanism is potent serotonin reuptake inhibition, with a secondary effect on norepinephrine, making it highly effective for OCD.
Established OCD Treatment: Clomipramine was the first drug approved for OCD and is recognized as a potent anti-obsessional agent, though it is often a second-line option.
Significant Side Effects: Common side effects include dry mouth, constipation, sedation, dizziness, and weight gain, which are often more severe than those of SSRIs.
Serious Safety Concerns: Important warnings include an increased risk of suicidal thoughts in young adults, cardiac toxicity in overdose, and the potential for serotonin syndrome.
Comparison with SSRIs: While possibly equally effective for OCD, its less favorable side effect and safety profile means that SSRIs are typically chosen as the initial treatment.

What Defines a Tricyclic Antidepressant?

Tricyclic antidepressants (TCAs) are an older class of psychiatric medications named for their unique three-ring chemical structure. They were among the first antidepressants to be developed and function primarily by blocking the reuptake of neurotransmitters, namely norepinephrine and serotonin, within the brain's synapses. By preventing these chemical messengers from being reabsorbed by nerve cells, TCAs increase the availability of these neurotransmitters, which can help regulate mood and anxiety levels.

Clomipramine (brand name Anafranil) fits squarely into this classification, and its chemical structure is a chlorinated analog of imipramine, another well-known TCA. Its unique pharmacology, particularly its potent effect on serotonin, makes it particularly effective for obsessive-compulsive disorder (OCD). While its efficacy is well-established, the side effect profile of TCAs often makes them a second-line treatment option in modern medicine, with SSRIs being the more common first choice due to generally better tolerability.

The Pharmacology Behind Clomipramine

Clomipramine's therapeutic effect is primarily driven by its dual action on key neurotransmitters. While many TCAs primarily target norepinephrine, clomipramine is distinguished by its strong inhibitory effect on serotonin reuptake. It does this by blocking the serotonin transporter (SERT), leading to increased serotonin levels in the synaptic cleft. This mechanism is a key reason for its effectiveness in treating OCD, a condition strongly linked to serotonin dysregulation.

Serotonin Reuptake Inhibition: Clomipramine is a potent blocker of serotonin reuptake. This effect is thought to be the main driver of its anti-obsessional properties.
Norepinephrine Reuptake Inhibition: Clomipramine's active metabolite, desmethylclomipramine, is a potent inhibitor of norepinephrine reuptake. This adds to its overall antidepressant effects, but also contributes to some of its side effects.
Other Receptor Interactions: Like other TCAs, clomipramine also interacts with several other receptors, including muscarinic, histaminic, and adrenergic receptors. These off-target effects are responsible for many of the common side effects associated with TCAs, such as dry mouth, blurred vision, and drowsiness.

Clomipramine vs. Modern Antidepressants (SSRIs)

In the treatment of OCD, clomipramine has historically been considered highly effective, sometimes even superior to SSRIs in certain meta-analyses. However, the advent of selective serotonin reuptake inhibitors (SSRIs) has shifted the standard of care for many conditions. SSRIs, like fluoxetine (Prozac) and sertraline (Zoloft), also increase serotonin levels but do so with a much more targeted action, resulting in a more favorable side effect profile.

Here is a comparison of clomipramine and SSRIs:


Feature	Clomipramine (TCA)	Selective Serotonin Reuptake Inhibitors (SSRIs)
Classification	Tricyclic Antidepressant (TCA)	Selective Serotonin Reuptake Inhibitor (SSRI)
Mechanism	Inhibits reuptake of serotonin (primarily) and norepinephrine, and affects other receptors	Selectively inhibits reuptake of serotonin
Primary Use	FDA-approved for OCD; off-label for depression, panic disorder	First-line for depression, anxiety disorders, and OCD
Side Effect Profile	Higher incidence of anticholinergic side effects like dry mouth, constipation, sedation, and cardiac risks	Generally more tolerable; common side effects include nausea, headache, and sleep disturbances
Safety in Overdose	Significantly more dangerous in overdose, with higher risk of fatal cardiac events	Generally safer in overdose compared to TCAs
First-Line Status	Usually considered a second-line treatment for OCD due to side effects	Often the first choice due to better tolerability

Clinical Uses and Important Considerations

Beyond its FDA-approved use for OCD in adults and children over 10, clomipramine has several important clinical applications. It is sometimes prescribed off-label for conditions such as major depressive disorder, panic disorder, and certain types of chronic pain. Its use is carefully managed by healthcare providers, particularly considering its side effect profile and potential for serious complications.

Common Side Effects

As noted in clinical trials, clomipramine is known for a range of side effects. Many are manageable, especially at lower doses, but some can be significant:

Dry mouth: A very common anticholinergic effect, often requiring management with gum or special lozenges.
Constipation: Another frequent anticholinergic side effect.
Drowsiness/Sedation: Can be pronounced, especially when first starting treatment.
Dizziness: Particularly when standing up (orthostatic hypotension).
Weight gain: A notable side effect reported in a significant number of users.
Sexual dysfunction: Including decreased libido and issues with ejaculation.

Serious Warnings and Precautions

Due to its potential for serious side effects, clomipramine requires careful monitoring by a healthcare professional. Key safety considerations include:

Black Box Warning: Like other antidepressants, clomipramine carries a warning about an increased risk of suicidal thoughts and behaviors in young adults.
Cardiac Risks: It can cause heart rhythm problems (QTc prolongation) and hypotension, and is generally avoided in patients with recent heart attacks.
Seizure Risk: The risk of seizures is higher with clomipramine, especially at higher doses.
Overdose Toxicity: An overdose can be fatal due to its cardiac effects.
Serotonin Syndrome: Combining clomipramine with other serotonergic drugs can lead to a potentially life-threatening condition called serotonin syndrome.
Abrupt Discontinuation: Stopping clomipramine suddenly can cause withdrawal symptoms like nausea, headache, and irritability; a gradual taper is necessary.

Conclusion

In conclusion, clomipramine is definitively a tricyclic antidepressant, belonging to an older class of psychiatric medications. Its powerful effect on serotonin reuptake has made it a gold standard for treating obsessive-compulsive disorder (OCD) for many years. While studies show its efficacy for OCD can be comparable to or even slightly better than modern SSRIs, its broader pharmacological action leads to a more significant and challenging side effect profile, including anticholinergic and cardiac risks. For this reason, SSRIs are often preferred as a first-line treatment for OCD and other conditions, reserving clomipramine for cases where initial therapies have proven ineffective. A thorough understanding of its benefits and risks is essential for both clinicians and patients considering this medication.

For comprehensive guidance on clomipramine, consult the official FDA Medication Guide for Anafranil.

Frequently Asked Questions

Clomipramine (Anafranil) is a tricyclic antidepressant primarily used to treat obsessive-compulsive disorder (OCD). It works by increasing the levels of serotonin and norepinephrine in the brain.

TCAs affect multiple neurotransmitter systems, including serotonin and norepinephrine, leading to a broader range of side effects. SSRIs (selective serotonin reuptake inhibitors) primarily target serotonin, which generally results in a cleaner side effect profile and better tolerability for many patients.

Even though clomipramine is highly effective for OCD, it is typically used as a second-line therapy because modern antidepressants (SSRIs) offer a similar level of efficacy with a more favorable side effect profile.

Common side effects include dry mouth, constipation, drowsiness, dizziness, increased appetite, weight gain, and sexual dysfunction. These are primarily due to its non-selective interaction with other receptors.

No, you should not stop clomipramine abruptly. Sudden discontinuation can lead to withdrawal symptoms such as dizziness, nausea, and headache. Your doctor will provide a plan for gradual tapering.

An overdose of clomipramine is significantly more dangerous than with SSRIs. It can be fatal due to serious cardiac effects, including arrhythmias and hypotension.

Clomipramine is FDA-approved for treating OCD in children aged 10 and older. However, it carries a boxed warning about the increased risk of suicidal thoughts and behaviors in younger patients.