Mood Stabilizers fluoxetine

Conventional antipsychotic drugs such as chlorpromazine and haloperidol have long been used in the treatment of acute mania. More recently, atypical antipsychotic drugs including aripiprazole, olanzapine, quetiapine, risperidone, and ziprasi-done have been approved for the treatment of bipolar mania or mixed mood episodes as monotherapy or in combination with mood-stabilizing drugs.25 Aripiprazole and olanzapine are also approved for maintenance therapy. The combination of olanzapine and fluoxetine is approved for treatment of bipolar depression. Quetiapine is approved for treatment of... 

Recent case reports have suggested that atypical antipsychotics may also benefit patients with PTSD. For example, low doses of risperidone in combination with an antidepressant or mood stabilizer were reported effective for nightmares and flashbacks in patients with treatment-refractory PTSD ( 292). Both clozapine and olanzapine have also been reported to reduce PTSD symptoms in patients with a co-morbid psychotic disorder ( 293, 294). Finally, olanzapine added to fluoxetine resulted in significant improvement of hyperarousal symptoms in a patient with treatment-refractory PTSD caused by severe childhood physical and sexual abuse (295). 

Another group of mood-stabilizing drugs that are also anticonvulsant agents have become more widely used than lithium. These include carbamazepine and valproic acid for the treatment of acute mania and for prevention of its recurrence. Lamotrigine is approved for prevention of recurrence. Gabapentin, oxcarbazepine, and topiramate are sometimes used to treat bipolar disorder but are not approved by FDA for this indication. Aripiprazole, chlorpromazine, olanzapine, quetiapine, risperidone, and ziprasidone are approved by FDA for the treatment of manic phase of bipolar disorder. Olanzapine plus fluoxetine in combination and quetiapine are approved for the treatment of bipolar depression. 

A third important CYP450 enzyme for antidepressants and mood stabilizers is 3A4. Some benzodiazepines (e.g., alprazolam and triazolam) are substrates for 3A4 (Fig. 6—17). Some antidepressants are 3A4 inhibitors, including the SSRIs fluoxetine and fluvoxamine and the antidepressant nefazodone (Fig. 6—18). Administration of a 3A4 substrate with a 3A4 inhibitor will raise the level of the substrate. For example, fluoxetine, fluvoxamine, or nefazodone will raise the levels of alprazolam or triazolam, requiring dose reduction of the benzodiazepine (Fig. 6—18). 

Dual effects were observed in a 44-year-old schizophrenic patient taking clozapine with both fluoxetine and sertraline for mood stabilization (46). Clinical and motor status improved with both fluoxetine and sertraline cognitive function improved with clozapine and fluoxetine, but was not sustained with sertraline. 

A 48-year-old woman unresponsive to fluoxetine (20-40 mg/day for 8 weeks) was given additional mirtazapine (30 mg/day) (49). Over the next month her depression remitted, but after taking the combined treatment for 7 weeks she slept less, spent more, and was more sociable than usual. She was also argumentative and agitated. Mirtazapine and fluoxetine were withdrawn and valproate introduced as a mood stabilizer. Within 2 weeks her mood had settled but she subsequently became depressed again. 

The manic episode here could have been due to mirtazapine alone or to the combination of fluoxetine and mirtazapine. The case also demonstrates the common clinical observation that when an antidepressant treatment has apparently caused mania, withdrawal of antidepressant therapy often results in re-emergence of depressive symptoms, even when mood stabilizer treatment has been introduced. 

Activation and agitation may represent the induction of a bipolar state, especially a mixed dysphoric bipolar II condition sometimes associated with suicidal ideation, and require the addition of lithium, a mood stabilizer or an atypical antipsychotic, and/or discontinuation of fluoxetine... 

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