Valproic acid bipolar affective disorder

The discovery of benzodiazepines is a story of serendipity and certainly one that is difficult to predictably reproduce as part of a drug discovery program. Regrettably (or fortuitously), this story of the benzodiazepines is not an isolated example. Valproic acid, an agent used to treat epilepsy, migraine, chronic pain, and bipolar affective disorder, was also discovered by accident. 

Antipsychotic drugs are also indicated for schizoaffective disorders, which share characteristics of both schizophrenia and affective disorders. No fundamental difference between these two diagnoses has been reliably demonstrated. They are part of a continuum with bipolar psychotic disorder. The psychotic aspects of the illness require treatment with antipsychotic drugs, which may be used with other drugs such as antidepressants, lithium, or valproic acid. The manic phase in bipolar affective disorder often requires treatment with antipsychotic agents, although lithium or valproic acid supplemented with high-potency benzodiazepines (eg, lorazepam or clonazepam) may suffice in milder cases. Recent controlled trials support the efficacy of monotherapy with atypical antipsychotics in the acute phase (up to 4 weeks) of mania, and olanzapine and quetiapine has been approved for this indication. 

Valproic acid is the drug of first choice for prophylaxis of bipolar affective disorder in the United States, despite the lack of robust clinical trial evidence in support of this indication. But treatment with valproic acid is easy to initiate (especially compared to lithium), it is well tolerated and its use appears likely to extend if the evidence-base expands. As the semisodium salt, valproic acid is licenced for use in the treatment of acute mania unresponsive to lithium. (Note sodium valproate, see p. 420, is unlicenced for this indication.)... 

I Advantages. Valproic acid is available in multiple dosage formulations. It has a wide therapeutic index and can be considered a broad-spectrum AED. It also may be useful in other neurologic or psychiatric disorders, including migraine headache and bipolar-affective disorder. 

Carbamazepine and Valproic acid iiy for treatment bipolar affective disorder with psychosis... 

C. Clinical Use Lithium carbonate is used in the treatment of bipolar affective disorder (manic-depressive disease). Maintenance therapy with lithium decreases manic behavior and reduces both the frequency and the magnitude of mood swings. Drug therapy with neuroleptics or benzodiazepines may also be required at the initiation of lithium treatment. Antidepressant drugs may be required adjunctively during maintenance. Alternative drugs of value in bipolar affective disorder include carbamazepine, clonazepam, gabapentin, and valproic acid. 

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. 

---