Clomipramine Side Effects

Not all side effects for clomipramine may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to clomipramine: oral capsule, oral tablet

In addition to its needed effects, some unwanted effects may be caused by clomipramine. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking clomipramine:

More common
  • Bladder pain
  • bloody or cloudy urine
  • blurred vision
  • body aches or pain
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • confusion
  • difficult, burning, or painful urination
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • excessive muscle tone
  • fear or nervousness
  • feeling sad or empty
  • fever
  • hearing changes
  • irritability
  • lower back or side pain
  • muscle stiffness, tension, or tightness
  • poor concentration
  • rhythmic movement of muscles
  • shortness of breath or troubled breathing
  • sneezing
  • tightness of the chest or wheezing
  • unusual tiredness or weakness
  • voice changes
Less common
  • Anger that is hard to control
  • breast enlargement
  • burning while urinating
  • changes in vision
  • chills
  • decrease in the frequency of urination
  • difficulty in passing urine (dribbling)
  • difficulty in speaking
  • dry mouth
  • fast, irregular, pounding, or racing heartbeat or pulse
  • headache, severe and throbbing
  • hyperventilation
  • irregular heartbeats
  • irritability
  • nausea or vomiting
  • numbness, tingling, pain, or weakness in the hands or feet
  • pain during sexual intercourse
  • panic attacks
  • paranoia
  • rapidly changing moods
  • restlessness
  • shaking
  • swelling of the face, fingers, feet, or lower legs

Some of the side effects that can occur with clomipramine may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Acid or sour stomach
  • blistering, crusting, irritation, itching, or reddening of the skin
  • change in taste
  • constipation
  • cracked, dry, or scaly skin
  • change in interest in sexual intercourse
  • diarrhea
  • dry skin
  • heartburn
  • hives or welts, skin rash
  • inability to have or keep an erection
  • increased interest in sexual intercourse
  • joint pain
  • pimples
  • redness of the face, neck, arms, and occasionally, upper chest
  • shakiness in the legs, arms, hands, or feet
  • stomach discomfort, upset, or pain
  • swelling
  • swollen joints
  • trembling or shaking of the hands or feet
Less common
  • Absent, missed, or irregular menstrual periods
  • breast pain
  • sores, ulcers, or white spots on the lips or tongue or inside the mouth

For Healthcare Professionals

Applies to clomipramine: oral capsule

Nervous system

Nervous system side effects including drowsiness, dizziness, sedation, and headache have been reported frequently. Anticholinergic effects have been reported frequently and include dry mouth, blurry vision, constipation, and urinary retention. Tremor, delirium, akathisia, a tardive dyskinesia- like syndrome, myoclonus, motor hyperactivity during sleep, sleep abnormalities, dystonic reactions, Tourettism, and seizures have also been reported.

Where a primary reason for discontinuation could be identified, most patients discontinued because of nervous system complaints (5.4%), primarily somnolence.

One study has suggested that sedation may occur in 87% of treated patients.

The manufacturer reports that the cumulative incidence of seizures during premarketing testing averaged 0.64% at 90 days and 1.45% at 365 days.

Nearly all selective serotonin reuptake inhibitors, mixed serotonin/norepinephrine reuptake inhibitors, and tricyclic antidepressants cause sleep abnormalities to some extent. These antidepressants have marked dose-dependent effects on rapid eye movement (REM) sleep, causing reductions in the overall amount of REM sleep over the night and delays the first entry into REM sleep (increased REM sleep onset latency (ROL)), both in healthy subjects and depressed patients. The antidepressants that increase serotonin function appear to have the greatest effect on REM sleep. The reduction in REM sleep is greatest early in treatment, but gradually returns towards baseline during long-term therapy; however, ROL remains long. Following discontinuation of therapy the amount of REM sleep tends to rebound. Some of these drugs (i.e., bupropion, mirtazapine, nefazodone, trazodone, trimipramine) appear to have a modest or minimal effect on REM sleep.


Cardiovascular side effects that have been associated with the use of tricyclic antidepressants have included orthostatic hypotension, tachycardia, QRS widening, other conduction abnormalities, malignant arrhythmias, and malignant hypertension.

Both antiarrhythmic and proarrhythmic effects have been reported in association with tricyclic therapy.

One study of the cardiovascular effects of clomipramine in 26 depressed patients suggested that clomipramine may produce variable and complex cardiac effects. The authors concluded that the drug is "generally well tolerated but it does present some degree of risk for the heart".

Caution should be exercised if clomipramine must be used in patients with cardiovascular disease.


Psychiatric side effects with use of this drug have included mania and hallucinations. Suicidal ideation, paradoxical aggressiveness, and mental status changes have also been reported with use of clomipramine and other tricyclic antidepressants.


A study of 26,005 antidepressant users has reported 3.6 times more upper GI bleeding episodes with the use of SSRI's relative to the population who did not receive antidepressant medications. Upper gastrointestinal tract bleeding was observed in 2.3 times more frequently in patients receiving clomipramine.

Where a primary reason for discontinuation could be identified, the second most frequent reason for discontinuation was digestive system complaints (1.3%), primarily nausea and vomiting.

Gastrointestinal side effects have included nausea, vomiting, dry mouth, and constipation.


General side effects including increased appetite and weight gain have been associated with the use of clomipramine.


Other side effects including withdrawal reactions involving both rebound worsening of preexisting psychiatric conditions and physiologic symptoms have been reported. Abrupt discontinuation may result in symptoms of withdrawal (such as nausea, headache, malaise, irritability and generalized CNS stimulation). Specific physiologic withdrawal symptoms may include nervousness, anxiety, restlessness, akathisia, nausea, malaise, sweating, salivation and seizures. Tachycardia has also been reported.

In one retrospective chart review of 352 patients who were supervised during tapering and discontinuation from serotonin reuptake inhibitor therapy, dizziness, lethargy, paresthesia, nausea, vivid dreams, irritability, and lowered mood were the most common symptoms reported. Patients with at least on qualitatively new symptom were defined in the clomipramine group at a rate of 30.8%.


Genitourinary side effects have been reported frequently and have included sexual dysfunction (involving anorgasmia, impotence and decreased libido). Urinary retention has also been reported.

Decreased nocturnal penile tumescence and delayed ejaculation have been reported.

One report has suggested that cyproheptadine may be beneficial in the treatment of clomipramine- induced anorgasmia.

Cases of spontaneous orgasm associated with yawning and clomipramine therapy have been reported.


Hematologic side effects have been rare and have included agranulocytosis and pancytopenia.


Endocrine side effects including hyponatremia (in association with the syndrome of inappropriate secretion of antidiuretic hormone) have been reported rarely. Hyperprolactinemia, galactorrhea and secondary amenorrhea have also been reported. A case of pancreatitis associated with clomipramine overdose has been reported.

Following the ingestion of 750 mg to 1,500 mg of clomipramine, a 48 year old female patient developed acute chemical pancreatitis and subsequent abdominal ileus. Serum lipase levels were elevated to 2,546 international units at one point, with a concomitant serum amylase of 112 international units. Two weeks after discontinuing clomipramine and resting the patient's gastrointestinal tract, the ileus and pancreatitis had resolved.


Hepatic side effects have been rare and have included elevated liver function tests and drug-induced hepatitis.


Dermatologic side effects have included sweating (common) and drug eruptions, photosensitivity, and contact allergy (rare).


Other side effects including neuroleptic malignant syndrome have been reported. One case of neuroleptic malignant syndrome in association with clomipramine (20 mg/day) has been reported. Symptoms including sweating, pyrexia, muscle rigidity, and urinary incontinence resolved with 48 hours after discontinuation of clomipramine and recurred upon rechallenge.


Metabolic side effects including dyslipidemia have been reported. Dyslipidemia (i.e., hypercholesterolemia, hypertriglyceridemia) was reported in a patient receiving clomipramine 150 mg daily. A case of clomipramine-induced diabetes has also been reported.

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