Bipolar disorder occurs when symptoms of mania or hypomania manifest in an individual. These can include racing thoughts, elevated mood, aggressiveness, delusions and paranoia. Bipolar disorder can also be complicated by comorbid diseases such as depression or attention deficit hyperactivity disorder (ADHD), which can make treatment more of a challenge. Mainstays of treatment are lithium, anticonvulsants (valproate and carbamazepine), and atypical antipsychotics (risperidone, ziprasidone, aripiprazole, olanzapine and clozapine). Each intervention carries its own adverse effect profile which must be weighed by the patient before starting a regimen.
Lithium
Side effects of lithium are often related to dose and concentrations of the drug, and as a result serum concentrations are usually monitored in patients on lithium therapy. Often the effects occur at therapeutic levels and these include hand tremor, dry mouth, altered taste perception, increased thirst and urination, nausea and vomiting, weight gain, sexual side effects (decreased libido, impotence), and diarrhea. The effects on the gastrointestinal system often resolve with time and spreading the dose out over the course of a day can help as well. Increased thirst and urination can herald the onset of a syndrome known as "nephrogenic diabetes insipidus," at which point lithium should be withdrawn and patient treated for symptoms.
Side effects of lithium that suggest toxic levels are visual disturbances, muscle weakness, abnormal movements, slurred speech, altered mental status, seizures and cardiac rhythm disturbances. Hypothyroidism is also a common adverse effect and often accompanies a goiter, or enlarged thyroid gland. Some of the most serious effects can occur to a developing fetus, and the use of lithium in the first trimester has been associated with defects of the developing cardiovascular system.
Valproate
Valproate can initially cause tremors, gastrointestinal effects such as diarrhea/nausea/vomiting, hair loss and sedation. More serious effects include pancreatitis, increased levels of ammonia (which can result in confusion), decreased amount or dysfunction of platelets, and decreased amount of white blood cells. The serious effects are typically quite rare, and long term patients are at risk for weight gain and deficiencies in mental cognition.
Carbamazepine
Carbamazepine initially causes a rash, and gastrointestinal effects very similar to valproate, along with nervous system deficits such as blurry vision, sedation, clumsiness and vertigo. More serious side effects include SIADH (resulting in low blood sodium levels), Steven-Johnson syndrome (a hypersensitivity syndrome marked by widespread rashes), slowed cardiac conduction and aplastic anemia. Aplastic anemia is failure of the bone marrow to replenish the red blood cells, white blood cells, and platelets and as a result is very dangerous. Thankfully it is not a common adverse effect.
Risperidone
Common adverse effects are dizziness (especially upon standing), headache, and extrapyramidal symptoms (EPS). EPS include dystonia (localized muscular contractions), parkinsonism (muscle rigidity, slowed movements, mask like facies), akathisia (internal feeling of restlessness), and most serious of all, tardive dyskinesia (repetitive, involuntary movements that occur most likely in the mouth or face and often times has no treatment). Long term increases in the levels of the hormone prolactin is possible and can be manifested by sexual side effects in men and absence of menstruation with nipple discharge in women. Weight gain with a risk of diabetes has also been noted in users of this medication.
Ziprasidone
Common effects involve the gastrointestinal system such as nausea or indigestion; and the nervous system such as sedation and headache. EPS are possible but much lower than other classes of medication and risperidone; and while cardiac arrhythmias have been noted, they have not been deemed serious enough to warrant frequent ECG monitoring.
Aripiprazole
Adverse effects include headache, gastrointestinal effects such as nausea and vomiting, and insomnia. Other than akathisia, EPS are relatively uncommon as are other side effects such as the weight gain, cardiac arrhythmia and increased prolactin levels noted in risperidone and ziprasidone.
Olanzapine
Users can suffer from constipation, dry mouth, dizziness, tremor, and EPS can occur albeit at much lower levels than other atypical antipsychotics. Metabolic effects predominate such as weight gain, significant risk of diabetes mellitus development and thus metabolic and cardiovascular monitoring is done by the clinician. Increased prolactin levels is also possible such as in other atypical antipsychotics but usually only occurs at higher doses.
Clozapine
Initially it has a wide array of side effects including dry mouth, constipation, sedation, and dizziness. Long term effects are similar to olanzapine with frequent weight gain, hyperlipidemia, and diabetes development. A serious side effect that can occur is agranulocytosis which is failure of the bone marrow to create white blood cells; thus monitoring of the white blood cell count is undertaken on those on clozapine therapy. Seizures are an additional risk of clozapine therapy.
References
- "Massachusetts General Hospital Comprehensive Clinical Psychiatry, 1st Edition;" Stern 2008
- "Conns Current Therapy 2009, 1st Edition;" Rakel & Bope; 2008
- Primary Care: Clinics in Office Practice. "Bipolar Spectrum Disorder: Differential Diagnosis and Treatment." Muzina D. Volume 34, Issue 3 (September 2007)
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