PHARMACOTHERAPY - I PHCY 310 University of Nizwa College of Pharmacy and Nursing School of Pharmacy PHARMACOTHERAPY - I PHCY 310 Lecture -16 Psychiatric Disorders “Bipolar disorders” Dr. Sabin Thomas, M. Pharm. Ph. D. Assistant Professor in Pharmacy Practice School of Pharmacy University of Nizwa

Bipolar disorder, previously known as manic-depressive illness, is a cyclical disorder with recurrent extreme fluctuations in mood, energy, and behavior. Diagnosis requires the occurrence of a manic, hypomanic, or mixed episode during the course of the illness. Classification Mood disorders are diagnosed using the criteria established in the Diagnostic and Statistical Manual of Mental Disorders, Fourth edition, Text Revision (DSM-IV-TR). Episodes of mood disturbances that the patient experience are determined to be major depressive episodes, manic episodes (episodes of elevated mood), mixed episodes (with features of both depression and mania), or hypomanic episodes.

Manic and hypomanic episodes are both characterized by a distinct period of abnormally and persistently elevated, expansive, or irritable mood. However, the hypomanic episodes are less intense than the manic episodes. Manic episodes are severe enough to impair functioning (self-care, occupational, social), complicate a medical condition, result in psychotic features, or require hospitalization. Pathophysiology Hormonal changes during the menstrual cycle, postpartum period, and perimenopausal phase may contribute to mood dysregulation.

L-tryptophan or 5-HT deficiency and changes in the light-dark cycle may result in reduced melatonin secretion from the pineal gland, which disrupts the sleep-wake cycle, alters circadian rhythms, and causes seasonal affective changes. Gama aminobutyric acid (GABA) deficiency hypothesis is proposed for mania since it inhibits NE (norepinephrine) and DA (dopamine)activity. Glutamate and aspartate, excitatory amino acid neurotransmitters, may be overactive and thus cause manic episodes. Cholinergic underactivity has been proposed to cause mania and overactivity of acetylcholine to cause depression.

MIXED EPISODE Mixed episodes occur in up to 40% of all episodes, are often difficult to diagnose and treat, and are more common in younger and older patients and females. Patients with mixed states often have comorbid alcohol and substance abuse, severe anxiety symptoms, a higher suicide rate, and a poorer prognosis. Risk factors for rapid cycling include biologic rhythm dysregulation, antidepressant or stimulant use, hypothyroidism, and premenstrual and postpartum states. Women are more likely to have mixed states, depressive episodes, and rapid cycling than men. Approximately 10% to 15% of adolescents with recurrent major depressive episodes subsequently have an episode of mania or hypomania.

Treatments of First Choice Lithium, divalproex sodium (valproate), aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone are currently approved by the FDA for treatment of acute mania in bipolar disorder. Lithium, olanzapine, and lamotrigine are approved for maintenance treatment of bipolar disorder. Quetiapine is the only antipsychotic that is FDA approved for bipolar depression. Lithium is the drug of choice for bipolar disorder with euphoric mania, whereas valproate has better efficacy for mixed states, irritable/dysphoric mania, and rapid cycling compared with lithium. Combination therapies (e.g., lithium plus valproate or carbamazepine; lithium or valproate plus an atypical antipsychotic) may provide better acute response and prevention of relapse and recurrence than monotherapy. If a patient responded well to a specific pharmacologic agent in the past and it was well tolerated, then use the same treatment again.

If a patient had intolerance or adverse reactions to a specific pharmacologic agent in the past or has a strong preference against an agent, then do not use it. It is preferable to slowly taper off a medication than to abruptly discontinue it. Alternative Treatments High potency benzodiazepines (e.g., clonazepam and lorazepam) are common alternatives to antipsychotics for agitation, anxiety, panic, and insomnia. A relative contraindication for long-term benzodiazepines is drug and alcohol abuse or dependency. Tricyclic antidepressants are associated with an increased risk of inducing mania in bipolar I disorder and possibly cause rapid cycling. High doses of levothyroxine sodium (0.15 to 0.4 mcg/day) have been reported to have mood stabilizing properties in rapid-cycling bipolar patients when combined with mood-stabilizing agents