Bipolar disorder benzodiazepines

Control of early withdrawal symptoms, which prevents their progression to more serious symptoms, is the indication for which medications are most widely prescribed in the treatment of alcohol dependence. The most commonly used agents to treat alcohol withdrawal are the benzodiazepines, a class of drugs that, by virtue of their agonist activity at the GABA receptor complex, suppress the hyperexcitability associated with alcohol withdrawal. With widespread use of anticonvulsant medications for bipolar disorder and other disorders associated with behavioral disinhibition and CNS hyperexcitability, anticonvulsants have also been examined for use in the treatment of alcohol withdrawal. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

Until recently, lithium carbonate was the universally preferred treatment for bipolar disorder, especially in the manic phase. With the approval of valproate, aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone for this indication, a smaller percentage of bipolar patients now receive lithium. This trend is reinforced by the slow onset of action of lithium, which has often been supplemented with concurrent use of antipsychotic drugs or potent benzodiazepines in severely manic patients. The overall success rate for achieving remission from the manic phase of bipolar disorder can be as high as 80% but lower among patients who require hospitalization. A similar situation applies to maintenance treatment, which is about 60% effective overall but less in severely ill patients. These considerations have led to increased use of combined treatment in severe cases. After mania is controlled, the antipsychotic drug may be stopped and benzodiazepines and lithium continued as maintenance therapy. 

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. 

Combination treatments for maintenance of bipolar disorder can include two or more mood stabilizers a mood stabilizer and an atypical antipsychotic a mood stabilizer and/or atypical antipsychotic with a benzodiazepine a mood stabilizer with thyroid hormone and even a mood stabilizer and/or atypical antipsychotic with an antidepressant (Fig. 7—35). 

FIGURE 11-52. Positive symptom pharmacy. First-line treatment of positive symptoms is now atypical antipsychotics (SDA), not only for schizophrenia but also for positive symptoms associated with bipolar disorder, Alzheimer s disease, childhood psychoses, and other psychotic disorders. However, conventional antipsychotics (D2) and benzodiazepines (BZ) are still useful for acute intramuscular administration (in case of emergency), and D2 for monthly depot injections for noncompliant patients, as well as for second-line use after several atypical agents fail. Clozapine (C), polypharmacy, and combinations (combos) are relegated to second- and third-line treatment for positive symptoms of psychosis. 

Catatonia was reported in a 48-year-old woman with bipolar disorder within 48 hours of withdrawal of gabapentin, 500 mg/day. The condition lasted for several days and disappeared after treatment with a benzodiazepine. 

Benzodiazepines are frequently used as augmenting agents for antipsychotics and mood stabilizers in the treatment of psychotic and bipolar disorders... 

One of the most popular and useful benzodiazepines for treatment of agitation associated with psychosis, bipolar disorder, and other disorders, especially in the inpatient setting this is due in part to useful sedative properties and flexibility of administration with oral tablets, oral liquid, or injectable formulations, which is often useful in treating uncooperative patients Is a very useful adjunct to SSRIs and SNRIs in the treatment of numerous anxiety disorders... 

Carbamazepine is licenced as an alternative to lithium for prophylaxis of bipolar affective disorder, although clinical trial evidence is actually stronger to support its use in the treatment of acute mania. Carbamazepine appears to be more effective than lithium for rapidly cycling bipolar disorders, i.e. with recurrent swift transitions from mania to depression. It is also effective in combination with lithium. Its mode of action is thought to involve agonism of inhibitory GABA transmission at the GABA-benzodiazepine receptor complex (see also Epilepsy, p. 417). 

Pharmacotherapy is crncial for the acute and maintenance treatment of bipolar disorder and inclndes lithium, valproate, carba-mazepine, oxcarbazepine, lamotrigine, atypical antipsychotics, and adjnnctive agents snch as antidepressants and benzodiazepines. 

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