Mood Stabilizers as Medications carbamazepine, Tegretol

Mood stabilizer: carbamazepine, Tegretol

Generic Name: carbamazepine
Brand Name(s): Tegretol
Common Use: Mood stabilizer

Carbamazepine has anticonvulsant properties which have been found useful in the treatment of psychomotor epilepsy and as an adjunct in the treatment of partial epilepsies, when administered in conjunction with other anticonvulsant drugs to prevent the possible generalization of the epileptic discharge. A mild psychotropic effect has been observed in some patients, which seems related to the effect of the carbamazepine in psychomotor or temporal lobe epilepsy.

Carbamazepine given as a monotherapy or in combination with lithium or neuroleptics has been found useful in the treatment of acute mania and the prophylactic treatment of bipolar (manic-depressive) disorders.

Like other tricyclic compounds, carbamazepine has a moderate anticholinergic action which is responsible for some of its adverse effects. A tolerance may develop to the action of carbamazepine after a few months of treatment and should be watched for.

Treatment of Acute Mania and Prophylaxis in Bipolar (Manic-Depressive) Disorders:
Carbamazepine may be used as a monotherapy or as an adjunct to lithium in the treatment of acute mania or prophylaxis of bipolar (manic-depressive) disorders in patients who are resistant to or are intolerant of conventional antimanic drugs. Carbamazepine may be a useful alternative to neuroleptics in such patients. Patients with severe mania, dysphoric mania or rapid cycling who are non-responsive to lithium may show a positive response when treated with carbamazepine. It is important to note that these recommendations are based on extensive clinical experience and some clinical trials versus active comparison agents.

Contraindications
Should not be administered to patients with a history of hepatic disease, acute intermittent porphyria or serious blood disorder.

The drug should not be administered immediately before, in conjunction with, or immediately after an MAO inhibitor. When it seems desirable to administer carbamazepine to a patient who has been receiving an MAO inhibitor, there should be as long a drug-free interval as the clinical condition allows, but in no case should this be less than 14 days. Then the dosage of carbamazepine should be low initially, and increased very gradually.

Adverse Effects
The reactions which have been most frequently reported with carbamazepine are CNS (e.g., drowsiness, headache, unsteadiness on the feet, diplopia, dizziness), gastrointestinal disturbances (nausea, vomiting), as well as allergic skin reactions. These reactions usually occur only during the initial phase of therapy, if the initial dose is too high, or when treating elderly patients. They have rarely necessitated discontinuing carbamazepine therapy and can be minimized by initiating treatment at a low dosage.

The occurrence of CNS adverse reactions may be a manifestation of relative overdosage or significant fluctuation in plasma levels. In such cases it is advisable to monitor the plasma levels and possibly lower the daily dose and/or divide it into 3 to 4 fractional doses. The more serious adverse reactions observed are the hematologic, hepatic, cardiovascular and dermatologic reactions, which require discontinuation of therapy. If treatment with carbamazepine has to be withdrawn abruptly, the change-over to another antiepileptic drug should be effected under cover of diazepam.

The following adverse reactions have been reported:
Occasional or frequent: Leukopenia. Occasional: Eosinophilia, thrombocytopenia. Rare: Leukocytosis, lymphadenopathy. Isolated cases: Agranulocytosis, aplastic anemia, pure red cell aplasia, macrocytic anemia, acute intermittent porphyria, reticulocytosis, folic acid deficiency, thrombocytopenic purpura, and possibly hemolytic anemia. In a few instances, deaths have occurred. Occasional to frequent: Skin sensitivity reactions and rashes, erythematous rashes, urticaria. Rare: Exfoliative dermatitis and erythroderma, Stevens-Johnson syndrome, systemic lupus erythematosus-like syndrome. Isolated cases: toxic epidermal necrolysis (Lyell's syndrome), photosensitivity, erythema multiform and nodosum, skin pigmentation changes, pruritus, purpura, acne, diaphoresis, alopecia and neurodermatitis. Frequent: Vertigo, somnolence, ataxia and fatigue. Occasionally: An increase in motor seizures (see Indications), headache, diplopia, nystagmus, accommodation disorders (e.g., blurred vision). Rare: Abnormal involuntary disorders (e.g., tremor, asterixis, orofacial dyskinesia, choreoathetosis disorders, dystonia, tics). Isolated cases: Oculomotor disturbances, speech disorders (e.g., dysarthria or slurred speech), peripheral neuritis, paresthesia. There have been some reports of paralysis and other symptoms of cerebral arterial insufficiency but no conclusive relationship to the administration of carbamazepine could be established. Disturbances of cardiac conduction, bradycardia, arrhythmias, Stokes-Adams in patients with AV block, congestive heart failure, hypertension or hypotension, aggravation of coronary artery disease, thrombophlebitis, thromboembolism. Some of these complications (including myocardial infarction and arrhythmia) have been associated with other tricyclic compounds. Isolated cases: Hallucinations (visual or acoustic), depression, sometimes with talkativeness, agitation, loss of appetite, restlessness, aggressive behaviour, confusion, activation of psychosis. Isolated cases: Interstitial nephritis and renal failure, as well as signs of renal dysfunction (e.g., albuminuria, glycosuria, hematuria, oliguria sometimes associated with elevated blood pressure, and elevated BUN/azotemia), urinary frequency, urinary retention and renal failure. Isolated reports: Sexual disturbances/impotence. Occasional or frequent: Nausea, vomiting. Occasional: Dryness of the mouth and throat. Rare: Diarrhea or constipation. Isolated cases: Abdominal pain, glossitis, stomatitis, anorexia. Isolated cases: Lens opacities, conjunctivitis, retinal changes, tinnitus, hyperacusis and taste disturbances. Occasionally edema, fluid retention, weight increase, hyponatremia and reduced plasma osmolality due to antidiuretic hormone (ADH)-like effect occurs, leading in isolated cases to water intoxication accompanied by lethargy, vomiting, headache, mental confusion and neurological abnormalities. Isolated cases of gynecomastia or galactorrhea have been reported, as well as abnormal thyroid function tests (decreased L-thyroxine, i.e., FT(4), T(4), T(3), and increased TSH, usually without clinical manifestations), disturbances of bone metabolism (decrease in plasma calcium and 25-OH-calciferol), leading in isolated cases to osteomalacia, as well as reports of elevated levels of cholesterol, including HDL cholesterol and triglycerides. Isolated cases: Arthralgia, muscle pain or cramp. Isolated cases: Pulmonary hypersensitivity characterized by fever, dyspnea, pneumonitis or pneumonia. A rare delayed multi-organ hypersensitivity disorder with fever, skin rashes, vasculitis, lymphadenopathy, disorders mimicking lymphoma, arthralgia, leukopenia, eosinophilia, hepato-splenomegaly and abnormal liver function tests, occurring in various combinations. Other organs may also be affected (e.g., lungs, kidneys, pancreas, myocardium). Isolated cases: Aseptic meningitis, with myoclonus and eosinophilia; anaphylactic reaction. Treatment should be discontinued should such hypersensitivity reactions occur.

Overdose

The presenting signs and symptoms of overdosage usually involve the central nervous, cardiovascular and respiratory systems. CNS depression, disorientation, tremor, restlessness, somnolence, agitation, hallucination, coma, blurred vision, nystagmus, mydriasis, slurred speech, dysarthria, ataxia, dyskinesia, abnormal reflexes (slowed/hyperactive), convulsions, psychomotor disturbances, myoclonus, opisthotonia, hypothermia/hyperthermia, flushed skin/cyanosis, EEG changes.There is no known specific antidote to carbamazepine.

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