Clomipramine Adverse Reactions
- abdominal pain
- agitation
- agranulocytosis
- akathisia
- anemia
- anorexia
- anxiety
- blurred vision
- breast enlargement
- confusion
- constipation
- cycloplegia
- diarrhea
- dizziness
- drowsiness
- EEG changes
- ejaculation dysfunction
- eosinophilia
- erythema
- fever
- galactorrhea
- gynecomastia
- heart failure
- hostility
- hypertension
- ileus
- impotence
- insomnia
- irritability
- jaundice
- leukopenia
- libido decrease
- mania
- mydriasis
- myocardial infarction
- nausea/vomiting
- ocular hypertension
- orgasm dysfunction
- orthostatic hypotension
- palpitations
- photosensitivity
- PR prolongation
- pruritus
- pseudoparkinsonism
- purpura
- QT prolongation
- seizures
- serotonin syndrome
- SIADH
- stroke
- suicidal ideation
- testicular swelling
- thrombocytopenia
- tremor
- urinary retention
- urticaria
- vasculitis
- ventricular tachycardia
- withdrawal
- xerostomia
Clomipramine Adverse Reactions
Suicidal ideation has been reported in patients participating in clinical trials with antidepressants. The symptoms of aggressiveness, akathisia (psychomotor restlessness), agitation, anxiety, insomnia, irritability, hostility, mania, hypomania, impulsivity, and panic attacks have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality. Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidal ideation. Changing or stopping the therapeutic regimen may be especially important if these symptoms are severe, abrupt in onset, or were not part of the patient’s presenting symptoms. Many of these adverse symptoms have been reported in clinical trials and have not always been associated with suicidality. Rapid discontinuation of many antidepressants may also result in some of these adverse CNS events.
A wide variety of cardiovascular side effects can result from the use of tricyclic antidepressants due to their direct quinidine-like action, their potent anticholinergic properties, and their ability to potentiate norepinephrine. Ventricular tachycardia, palpitations, hypertension, and orthostatic hypotension all can be precipitated, with the possibility of more severe reactions occurring such as myocardial infarction, congestive heart failure, or stroke. Imipramine, and possibly other tricyclic antidepressants, can cause both PR prolongation and QT prolongation. Imipramine and nortriptyline are known to prolong the QRS interval. Other tricyclics would be expected to produce similar ECG changes. The cardiovascular response to tricyclic antidepressants depends on the specific agent and the dose. Although all tricyclic antidepressants are thought to be proarrhythmic after acute overdoses, at therapeutic doses, their actions on the conducting system of the heart may vary. Imipramine has been utilized therapeutically for its antiarrhythmic effect. The cardiovascular response to tricyclic antidepressants is varied, and patients most at risk have preexisting cardiovascular disease.
Drowsiness is the most frequent adverse CNS effect during therapy with tricyclic antidepressants. In clinical trials with clomipramine, sedation was the most common reason why patients discontinued therapy. Sedation may occur in 50% or more of patients receiving clomipramine. Sedation can be made into a desirable effect by administration of the tricyclic antidepressant at bedtime, which minimizes undesirable drowsiness during the day. Dizziness is usually due to orthostatic hypotension and can be reduced by having the patient change positions more slowly. Some patients exhibit excitation and anxiety. Confusion is most apparent in the elderly.
Peripheral nervous system adverse reactions can occur during therapy with tricyclic antidepressants. Tremor can result from norepinephrine reuptake blockade. Rarely, extrapyramidal symptoms can occur in both young and elderly patients. Pseudoparkinsonism is more likely to occur in the elderly, especially if they are receiving high doses.
Seizures and EEG changes have been observed more commonly in children than in adults during therapy with tricyclic antidepressants. Patients who have a preexisting seizure disorder may require increased concentrations of their anticonvulsant to maintain seizure control. There is a high incidence of seizures (2.1%) at doses greater than 300 mg per day.
Ocular manifestations of the anticholinergic actions of the tricyclic antidepressants include blurred vision due to cycloplegia, mydriasis, and increased intraocular pressure. Ocular hypertension can precipitate a crisis in patients with angle-closure glaucoma. Ophthalmological examination is recommended when there are visual changes.
Gastrointestinal manifestations of the anticholinergic activity of tricyclic antidepressants include dry mouth (xerostomia), constipation, urinary retention, adynamic ileus, abdominal pain or cramps, nausea/vomiting, anorexia, diarrhea, and jaundice. Constipation is more commonly observed in elderly patients. If these symptoms become severe, they can necessitate the discontinuation of the drug. In clinical trials with clomipramine, nausea/vomiting was the second most common reason patients discontinued therapy, second only to drowsiness. Nausea may occur in up to one-third of patients receiving clomipramine. Seven percent of patients experienced vomiting in studies.
Allergic reactions to tricyclic antidepressants can include photosensitivity, vasculitis, erythema, urticaria, fever, and/or pruritus. Fever also can indicate a blood dyscrasia.
The effects of tricyclic antidepressants on the endocrine system can cause sexual dysfunction including libido decrease, impotence, testicular swelling, ejaculation dysfunction (no, retarded or painful ejaculation), orgasm dysfunction, orgasm precipitated by yawning, breast enlargement, and galactorrhea in females or gynecomastia in males. Clomipramine also has been associated with involuntary orgasm during yawning. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported. Glucose metabolism can be altered and should be monitored in patients with diabetes mellitus.
Clomipramine may cause hematologic adverse reactions. These effects include agranulocytosis, eosinophilia, purpura, thrombocytopenia, anemia, and leukopenia.
Patients receiving prolonged therapy with high doses of tricyclic antidepressants can experience withdrawal symptoms following abrupt discontinuation of the tricyclic antidepressant. Symptoms of cholinergic rebound such as nausea, vomiting, or diarrhea can occur. This particularly occurs with the tertiary amine tricyclic antidepressants: amitriptyline, imipramine, clomipramine, trimipramine, and doxepin.
Very rare cases of serotonin syndrome have been reported when tricyclic antidepressants are administered concomitantly with other medications known to cause serotonin syndrome, particularly with SSRIs. Tricyclic antidepressants act, in part, as inhibitors of serotonin reuptake.
[ Last revised: 11/9/2005 12:35:00 PM ]
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