Neuroleptics bipolar disorder

Depression and mania are both affective disorders but their symptoms and treatments are quite distinct. Mania is expressed as heightened mood, exaggerated sense of self-worth, irritability, aggression, delusions and hallucinations. In stark contrast, the most obvious disturbance in depression is melancholia that often co-exists with behavioural and somatic changes (Table 20.1). Some individuals experience dramatic mood swings between depression and mania. This is known as "bipolar disorder which, like mania itself, is treated with lithium salts or neuroleptics. 

Despite the widespread use of neuroleptics in maintenance treatment of bipolar disorder, there have not been any systematic studies of their suitability for this role. Through clinical experience it has been widely accepted that neuroleptics are useful adjunctive treatments to lithium and related drugs. Treatment refractory patients frequently respond to atypical antipsychotics such as clozapine or risperidone. Such adverse effects as EPS, cognitive dysfunction and weight gain frequently limit the long-term use of classical neuroleptics. For this reason, the atypical neuroleptics such as olanzapine and risperidone should now be considered as alternatives for maintenance treatment. 

The primary indication for ECT in adolescents is the short-term treatment of mood symptoms, depressive or manic (Walter et al., 1999). Mood symptoms in the course of major depression, psychotic depression, bipolar disorder, organic mood disorders, schizophrenia, and schizoaffective disorder respond well to ECT. Psychotic symptoms in mood disorders also respond well to ECT whereas the effectiveness of ECT in the treatment of psychotic symptoms in schizophrenia is doubtful. There are suggestions that other uncommon clinical conditions in adolescents such as catatonia and neuroleptic malignant syndrome also benefit from ECT. The effectiveness of ECT seems to lessen when there is a comorbid personality disorder or drug and/or alcohol problems. There are very few data about usefulness on prepubertal children. 

The main indications for atypical antipsychotics are the acute and maintenance treatment of schizophrenic disorders, with an emphasis on the treatment of refractory and chronic disorders. However, because of the lower risk of EPS and in particular of tardive dyskinesia, there is a tendency toward a wider range of indications for some of the atypical neuroleptics. Favorable effects in drug-induced psychoses have been demonstrated for olanzapine. Clozapine seems effective in the treatment and relapse prevention of manic episodes and bipolar disorders, and risperidone has been shown to have good efficacy in conduct disorders and in the pervasive developmental disorders. 

FIGURE 7—35. Combination treatments for bipolar disorder (bipolar combos). Combination drug treatment is the rule rather than the exception for patients with bipolar disorder. It is best to attempt monotherapy, however, with first-line lithium or valproic acid, with second-line atypical antipsychotics, or with third-line anticonvulsant mood stabilizers. A very common situation in acute treatment of the manic phase of bipolar disorder is to treat with both a mood stabilizer and an atypical antipsychotic (atypical combo). Agitated patients may require intermittent doses of sedating benzodiazepines (benzo assault weapon), whereas patients out of control may require intermittent doses of tranquil-izing neuroleptics (neuroleptic nuclear weapon). For maintenance treatment, patients often require combinations of two mood stabilizers (mood stabilizer combo) or a mood stabilizer with an atypical antipsychotic (atypical combo). For patients who have depressive episodes despite mood stabilizer or atypical combos, antidepressants may be required (antidepressant combo). However, antidepressants may also decompensate patients into overt mania, rapid cycling states, or mixed states of mania and depression. Thus, antidepressant combos are used cautiously. 

Neuroleptics are used primarily in managing the symptoms of schizophrenia, although they are also used to treat a variety of conditions, including autism, attention deficit hyperactivity disorder (ADHD), bipolar disorder, and even to alleviate severe pain. 

The atypical neuroleptics—or new generation neuroleptics—cause fewer adverse side effects, are more effective in managing the symptoms of schizophrenia, and are effective for the treatment of bipolar disorder with or without psychosis. However, these drugs are cost more than the older medications. The five approved in the United States as of 2002 are ... 

In terms of approved medical use, the neuroleptics are often prescribed for children with autism, attention-deficit hyperactivity disorder (ADHD), and Tourette s syndrome. In addition, the popularity of the newer atypical neuroleptics for childhood bipolar disorder is growing rapidly, and sometimes these drugs are the only treatment offered. The neuroleptics are also commonly prescribed for the elderly in nursing homes or other insti-... 

While neuroleptics can effectively treat the depression present in bipolar disorder, the metal ion lithium exerts a therapeutic effect on the other aspect it relieves the... 

Chapter 10 will examine one of the great shames of my profession of psychiatry the increasing numbers of children diagnosed with bipolar disorder and medicated with adult mood stabilizers and neuroleptics. 

The benefits of the atypical neuroleptic drugs in patients with bipolar disorder and the possibility that risperidone, quetiapine, olanzapine, and clozapine cause... 

A 19-year-old man with bipolar disorder received intramuscular haloperidol 30 mg/day and chlorproma-zine 300 mg/day and developed neuroleptic malignant syndrome the neuroleptic drugs were withdrawn. One month later he had a recurrence. It transpired that he had discontinued his medication 2 weeks after discharge, but because his manic symptoms recurred his relatives had started to give him haloperidol 10 mg/day again, which led to the recurrence. 

A 67-year-old man with bipolar disorder became confused, delirious, and manic (99). His only medications were olanzapine 10 mg/day and divalproex sodium 500 mg bd. On day 6, typical neuroleptic malignant syndrome developed. He had a fever (39.9°C), obtundation, rigidity, tremor, sweating, fluctuating pupillary diameter, labile tachycardia and hypertension, hypernatremia, and raised serum creatine kinase. Olanzapine was withdrawn and the syndrome resolved by day 12. 

A number of unapproved uses of antipsy- chotic drugs also exist. CPZ and haloperidol were used early on to treat phencyclidine (PCP)-induced psychosis. Psychoses associ- ated with depression, bipolar disorder, and Alzheimer s disease are commonly treated with haloperidol, risperidone, or olanzapine. Psychotic symptoms in Parkinson s disease patients caused by levodopa and/or dopaminergic agonists have been alleviated with quetiapine, because EPS-prone typical neuroleptics contraindicated in Parkinson s disease. 

Antipsychotic drugs commonly have been used empirically to manage manic and psychotic illness in bipolar disorder patients. Indeed, standard neuroleptics are a mainstay of the treatment of acute mania (only chlorpromazine is FDA-approved for this indication, although haloperidol has also been widely used) and for manic episodes that break through prophylactic treatment with LF or an anticonvulsant. However, the older antipsychotics are not used routinely for long-term prophylactic treatment in bipolar disorder because their effectiveness is untested, some may worsen depression, and the risk of tardive dyskinesia in these syndromes may be higher than in schizophrenia. 

Sovner (1989) reported that five individuals with bipolar mood disorder responded to standard treatment with divalproex sodium after failing treatment with neuroleptics and/or carbamazepine. A recent retrospective review of divalproex treatment in 28 adults with MR and severe behavior problems showed improvement (Ruedrich et ah, 1999). 

Initially, the neuroleptics were used to manage severe anxiety, agitation, and aggression in individuals with severe mental illness such as schizophrenia, a psychotic illness characterized by delusions, hallucinations, and disorganized, illogical thinking. The first neuroleptic used in schizophrenia was chlorpromazine (Thorazine) in 1952. Additional neuroleptics were later developed to treat a variety of other disorders and conditions in children and adults, including autism, attention-deficit hyperactivity disorder (ADHD), bipolar dis-... 

In addition to Wilson et al. (1983), several other studies reported an association between TD symptoms and generalized mental dysfunction (Baribeau et al., 1993 DeWolfe et al., 1988 Itil et al., 1981 Spohn et al., 1993 Struve et al., 1983 Waddington et al., 1986a b Wolf et al., 1982 many reviewed in Breggin, 1993). After eliminating schizophrenia as a causative factor, Waddington and Youssef (1988) also found increased cognitive deficits in neuroleptic-treated bipolar patients with TD in comparison to those without the disorder. 

Meyer-Lindenberg, A., Krausmck, B. (1997). Tardive dyskinesia in a neuroleptic-naive patient with bipolar-I disorder Persistent exacerbation after lithium intoxication. Movement Disorders, 12, 1108. 

Waddington, J., 8c Youssef, H. (1988). Tardive dyskinesia in bipolar affective disorder Aging, cognitive function, course of illness, and exposure to neuroleptics and lithium. American Journal of Psychiatry 145, 613-616. 

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