Medications

Side Effects. Although atypical antipsychotics have fewer severe side effects than standard antipsychotics, many patients fail to comply with regimens containing them. Common side effects include the following:

• Nasal congestion or runny nose
• Drooling
• Dizziness
• Headache
• Drowsiness -- however, these drugs may also cause restlessness and insomnia.
• Constipation
• Rapid heart beat
• Difficulty urinating
• Skin rash
• Increased body temperature
• Confusion, short-term memory problems, disorientation, and impaired attention
• Weight gain -- risk is highest with clozapine and olanzapine.

Atypicals also have some rare but serious side effects:

• Diabetes. All atypical antipsychotics can increase the risk of elevated blood sugar (hyperglycemia) and diabetes. The risk is highest for clozapine and olanzapine. All patients treated with atypical antipsychotics should receive a baseline blood sugar level reading and be monitored for any increases in blood sugar levels during drug treatment.
• Seizures. There is a 5% risk per year with clozapine. Others pose less of a risk.
• Heat stroke. People who take atypicals have a higher risk of heat stroke.
• Extrapyramidal effects, which are lack of motor coordination and involuntary movements.
• The risk for cataracts increases. Existing glaucoma may get worse.
• Prolactin levels may be increased. Prolactin is a hormone that can cause fluid secretions from breasts in women or impotence in men. Women with increased prolactin levels have a higher risk for breast cancer.
• Heart problems, including arrhythmias, have been reported with initial usage of the drug. The risk for abnormal heart rhythms appears to be highest with clozapine and olanzapine, moderate with risperidone, and low with quetiapine.
• Agranulocytosis is a potentially life-threatening reduction in certain white blood cells. This complication occurs in about 1% of people taking clozapine, most often after 3 months of treatment, and peaks in the third month. This complication can be reversed if the drug is withdrawn at once. Older women are at higher risk.

Antidepressants

Antidepressants are sometimes used for depressive episodes in bipolar disorder, but their use is controversial. They trigger mania in 12 - 28% of patients. In addition, a number of studies report no additional benefits from antidepressants. A 2002 study suggested that they may be helpful for patients whose depression occurs after an episode-free period (rather than after a manic or hypomanic episode.) Specific antidepressants may be beneficial in certain circumstances. However, any patient on antidepressants who develops symptoms of hypomania should stop taking these drugs, since hypomania is often a sign of impending mania. All antidepressants should be tapered off after the mood has been stabilized for a month.

Bupropion. The antidepressant bupropion (Wellbutrin) appears to pose a lower risk for triggering mania than do other antidepressants. Side effects include restlessness, agitation, sleeplessness, headache, rashes, stomach problems, and in rare cases, hallucinations and bizarre thinking. Initial weight loss occurs in about 25% of patients. High doses may cause seizures. This side effect is uncommon and tends to occur in patients with eating disorders (anorexia or bulimia) or those with risk factors for seizures.

Selective Serotonin Reuptake Inhibitors. Serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), citalopram (Celexa), sertraline (Zoloft), and paroxetine (Paxil), are sometimes used to treat bipolar depression, but their benefits have not yet been established. They may be useful in patients whose depression does not respond to lithium. They do not appear to be useful as an add-on treatment to lithium. (A newer "designer antidepressant," venlafaxine (Effexor), may also be used in patients with severe cases of depression who do not respond to other treatments.) Side effects of SSRIs include:

• Nausea and gastrointestinal problems, which usually wear off over time
• Agitation, insomnia, mild tremor, and impulsivity
• Dry mouth, which can increase the risk for cavities and mouth sores
• Headache
• Sexual dysfunction

Some weight loss may occur during the first few weeks of treatment, but over time patients on maintenance treatment typically return to their pretreatment weight.

Monoamine Oxidase Inhibitors (MAOIs). Older drugs known as monoamine oxidase inhibitors (MAOIs), particularly tranylcypromine (Parnate) are recommended for depression that does not respond to newer antidepressants. MAOIs can interact with certain foods and cause severe high blood pressure. Such foods have high tyramine content and include aged cheeses, most red wines, vermouth, dried meats and fish, canned figs, fava beans, and concentrated yeast products. MAOIs can also have severe interactions with certain drugs, including some common over-the-counter cough medications. In such cases, severe high blood pressure or dangerous reactions can occur. It is important that patients discuss with their doctor any other medications they are taking.

Calcium-Channel Blockers

Calcium-channel blockers are drugs commonly used for treating angina and high blood pressure. They also have nerve-protecting properties. Several studies indicate that at least one of these drugs -- verapamil (Calan, Isoptin, Verelan) -- has anti-manic and possibly mood-stabilizing effects. In a 2002 study, all patients with mania or hypomania reported at least a 50% improvement in their symptoms. In addition, 78% of patients with mixed states reported that mania improved and 39% of patients with depression and no mania or hypomania improved. Other calcium channel blockers, such as nimodipine (Nimotop), may help treat ultra-rapid cycling. Nimodipine has been shown to reduce hypomania and may work particularly well when added to carbamazepine.

These drugs do not cause mental dysfunction, sedation, or weight gain as do other bipolar drugs. They may be safer during pregnancy and breastfeeding. Their side effects can include fluid build-up in the feet, constipation, fatigue, impotence, gingivitis, flushing, and allergic symptoms. Overdose can cause a severe drop in blood pressure. Note: Grapefruit and Seville (sour) oranges boost the effects of calcium-channel blocking drugs. (Regular oranges do not appear to pose any problems.)