From the Guidelines
Clomipramine is associated with several side effects, including nausea, dry mouth, drowsiness, and reduced libido.
Common Side Effects
- Nausea
- Dry mouth
- Drowsiness
- Reduced libido These side effects are similar to those reported in patients being treated for depression, and are generally considered acceptable to most patients 1.
Serious Side Effects
- Mania
- Withdrawal symptoms
- Serotonergic syndrome (characterized by headache, nausea, sweating, and dizziness, and in severe cases, hyperthermia, rigidity, delirium, and coma) These serious side effects are rare, but can occur, especially with concomitant use of other medications such as monoamine oxidase inhibitors, lithium, sumatriptan, and tryptophan 1.
Dose-Related Side Effects
The adverse event rates and beneficial effects of clomipramine appear to be dose-related, with higher doses associated with increased efficacy, but also with higher rates of dropout due to adverse effects 1.
Comparison to Other Medications
Clomipramine has a higher risk of side effects compared to selective serotonin reuptake inhibitors (SSRIs), which have a higher safety and tolerability profile 1.
Special Considerations
Patients should be advised to avoid sudden cessation or rapid dose reduction of daily dosed clomipramine, as this may precipitate withdrawal syndrome 1. Additionally, treatment with clomipramine should be avoided in men with a history of bipolar depression due to the risk of mania 1.
From the FDA Drug Label
The most commonly observed adverse events associated with the use of clomipramine hydrochloride and not seen at an equivalent incidence among placebo-treated patients were gastrointestinal complaints, including dry mouth, constipation, nausea, dyspepsia, and anorexia; nervous system complaints, including somnolence, tremor, dizziness, nervousness, and myoclonus; genitourinary complaints, including changed libido, ejaculatory failure, impotence, and micturition disorder; and other miscellaneous complaints, including fatigue, sweating, increased appetite, weight gain, and visual changes.
Approximately 20% of 3616 patients who received clomipramine hydrochloride in U. S. premarketing clinical trials discontinued treatment because of an adverse event.
The following table enumerates adverse events that occurred at an incidence of 1% or greater among patients with OCD who received clomipramine hydrochloride in adult or pediatric placebo-controlled clinical trials
Rare – aneurysm, atrial flutter, bundle branch block, cardiac failure, cerebral hemorrhage, heart block, myocardial infarction, myocardial ischemia, peripheral ischemia, thrombophlebitis, vasospasm, ventricular tachycardia
Infrequent – abnormal hepatic function, blood in stool, colitis, duodenitis, gastric ulcer, gastritis, gastroesophageal reflux, gingivitis, glossitis, hemorrhoids, hepatitis, increased saliva, irritable bowel syndrome, peptic ulcer, rectal hemorrhage, tongue ulceration, tooth caries
Rare – cheilitis, chronic enteritis, discolored feces, gastric dilatation, gingival bleeding, hiccup, intestinal obstruction, oral/pharyngeal edema, paralytic ileus, salivary gland enlargement.
The side effects of clomipramine (Anafranil) include:
- Gastrointestinal complaints: dry mouth, constipation, nausea, dyspepsia, anorexia
- Nervous system complaints: somnolence, tremor, dizziness, nervousness, myoclonus
- Genitourinary complaints: changed libido, ejaculatory failure, impotence, micturition disorder
- Miscellaneous complaints: fatigue, sweating, increased appetite, weight gain, visual changes
- Cardiovascular events: aneurysm, atrial flutter, bundle branch block, cardiac failure, cerebral hemorrhage, heart block, myocardial infarction, myocardial ischemia, peripheral ischemia, thrombophlebitis, vasospasm, ventricular tachycardia
- Digestive system events: abnormal hepatic function, blood in stool, colitis, duodenitis, gastric ulcer, gastritis, gastroesophageal reflux, gingivitis, glossitis, hemorrhoids, hepatitis, increased saliva, irritable bowel syndrome, peptic ulcer, rectal hemorrhage, tongue ulceration, tooth caries
- Other events: cheilitis, chronic enteritis, discolored feces, gastric dilatation, gingival bleeding, hiccup, intestinal obstruction, oral/pharyngeal edema, paralytic ileus, salivary gland enlargement 2 2
From the Research
Side Effects of Clomipramine
The side effects of clomipramine (Anafranil) are well-documented in various studies 3, 4, 5, 6, 7. Some of the common side effects include:
- Anticholinergic effects, such as dry mouth, constipation, and visual disturbances 4, 5, 7
- Cardiovascular effects, such as orthostasis and cardiotoxicity 4, 7
- Sexual dysfunction, including decreased libido and impotence 4, 5, 7
- Central nervous system effects, such as somnolence, tremors, and dizziness 4, 5, 6
- Gastrointestinal effects, such as nausea and diarrhea 6
- Seizures, which can occur in a dose-related manner, with a higher incidence at doses above 250 mg/day 3, 7
Serious Side Effects
Some of the more serious side effects of clomipramine include:
- Increased risk of seizures, particularly at high doses 3, 7
- Cardiotoxicity, which can be life-threatening in some cases 4, 7
- Overdose risk, which can be considerable due to the drug's narrow therapeutic index 4
Comparison with Other Medications
Studies have compared the side effect profiles of clomipramine with other medications, such as sertraline 6. These studies have found that clomipramine is associated with a higher incidence of certain side effects, such as dry mouth, anxiety, and constipation, compared to sertraline. However, clomipramine has also been shown to be effective in treating obsessive-compulsive disorder (OCD) and other conditions, making it a valuable treatment option for some patients 3, 4, 5, 7.