Mental retardation with bipolar disorders

The dibenzapine derivatives are called tricyclic antidepressants and include imipramine (Tofranil), desipramine (Norpramin), amitriptyline (Elavil), nortriptyline (Aventyl), protriptyline (Vivactil), and doxepin (Adapin). Amitriptyline is indicated in depression major depression with melancholia or psychotic symptoms depressive phase of bipolar disorder depression associated with organic disease, alcoholism, schizophrenia, or mental retardation anorexia or bulimia associated with depression (see Figure 20). 

According to the Expert Consensus Panel for Mental Retardation Rush and Frances, (2000), the mainstays of the pharmacological treatment of acute mania or bipolar disorder in adults are anticonvulsant medications (divalproex, valproic acid, or carbamazepine) or lithium. Both divalproex or valproic acid and lithium were preferred treatments for classic, euphoric manic episodes. Divalproex or valproic acid was preferred over lithium and carbamazepine for mixed or dysphoric manic episodes and rapid-cycling mania. For depressive episodes associated with bipolar disorder, the addition of an antidepressant (SSRI, bupropion, or venlafaxine) was recommended. According to the Expert Consensus Panel, the presence of MR does not affect the choice of medication for these psychiatric disorders in adults. 

Sovner, R. (1989) The use of valproate in the treatment of mentally retarded persons with typical and atypical bipolar disorders. J Clin Psychiatry 50 40—43. 

Serious hepatotoxicity is possibie but rare. Hepatic failure occurs in only one in 40,000 cases and appears to be an idiosyncratic reaction that is not dose-related. Children under the age of 2, especially those receiving anticonvulsant polypharmacy, with mental retardation, and/or with poor nutritional status have been shown to be at greatest risk (351, 352). To our knowledge, no cases of hepatic failure have been reported in adults with bipolar disorder who were receiving VPA monotherapy, but liver failure has been reported in older children and in a mentally retarded adult with epilepsy taking VPA alone ( 77, 352, 353). 

The efficacy and safety of risperidone have been examined in special groups of patients, such as those with psychotic depression (4), autistic disorders (41), bipolar disorder (5), mental retardation (6), and children and adolescents (7). 

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

Predictors of a positive response with valproate include rapid cycling, mixed episodes, comorbid panic disorder, organic mental disorders (e.g., head trauma), and mental retardation. " Low-dose valproate (125 to 500 mg/day) has been reported to be effective in reducing mood cycling in bipolar II disorder and cyclothymia. Oral loading with divalproex sodium, 20 mg/kg per day, may produce a rapid reduction in manic and psychotic symptoms within 4 days without causing major side effects, although there may be a lag time to obtain full antimanic efficacy. Development of tolerance and loss of efficacy with valproate occurs in some patients after several years of treatment." ... 

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