Mood-Stabilizing Drugs - Psychopharmacology

Mood-Stabilizing Drugs

Mood-stabilizing drugs are used to treat bipolar disorder by stabilizing the client’s mood, preventing or minimizing the highs and lows that characterize bipolar illness, and treating acute episodes of mania. Lithium is the most established mood stabilizer; some anticonvulsant drugs, particularly carbamazepine (Tegretol) and valproic acid(Depakote, Depakene), are effective mood stabilizers. Other anticonvulsants, such as gabapentin (Neurontin), topiramate (Topamax), oxcarbazepine (Trileptal), and lamotrigine (Lamictal), are also used for mood stabilization. Occasionally, clonazepam (Klonopin) also is used to treat acute mania. Clonazepam is included in the discussion of antianxiety agents.

Mechanism of Action

Although lithium has many neurobiologic effects, its mechanism of action in bipolar illness is poorly under-stood. Lithium normalizes the reuptake of certain neurotransmitters such as serotonin, norepinephrine, ace-tylcholine, and dopamine. It also reduces the release of norepinephrine through competition with calcium and produces its effects intracellularly rather than within neu-ronal synapses; it acts directly on G proteins and certain enzyme subsystems such as cyclic adenosine monophos-phates and phosphatidylinositol. Lithium is considered a first-line agent in the treatment of bipolar disorder (Howland, 2007).

The mechanism of action for anticonvulsants is not clear because it relates to their off-label use as mood stabilizers. Valproic acid and topiramate are known to increase levels of the inhibitory neurotransmitter GABA. Both valproic acid and carbamazepine are thought to stabilize mood by inhibiting the kindling process. This can be described as the snowball-like effect seen when minor seizure activity seems to build up into more frequent and severe seizures. In seizure management, anticonvulsants raise the level of the threshold to prevent these minor seizures. It is sus-pected that this same kindling process also may occur in the development of full-blown mania with stimulation by more frequent, minor episodes. This may explain why anti-convulsants are effective in the treatment and prevention of mania as well (Plata-Salaman et al., 2005).

Dosage

Lithium is available in tablets, capsules, liquid, and a sustained-released form; no parenteral forms are available. The effective dosage of lithium is determined by monitor-ing serum lithium levels and assessing the client’s clinical response to the drug. Daily dosages generally range from 900 to 3,600 mg; more importantly, the serum lithium level should be about 1.0 mEq/L. Serum lithium levels of less than 0.5 mEq/L are rarely therapeutic, and levels of more than 1.5 mEq/L are usually considered toxic. The lithium level should be monitored every 2 to 3 days while the therapeutic dosage is being determined; then, it should be monitored weekly. When the client’s condition is stable, the level may need to be checked once a month or less frequently.

Carbamazepine is available in liquid, tablet, and chewable tablet forms. Dosages usually range from 800 to 1,200 mg/ day; the extreme dosage range is 200 to 2,000 mg/day. Valproic acid is available in liquid, tablet, and capsule forms and as sprinkles with dosages ranging from 1,000 to 1,500 mg/day; the extreme dosage range is 750 to 3,000 mg/ day. Serum drug levels, obtained 12 hours after the last dose of the medication, are monitored for therapeutic levels of both these anticonvulsants.

Side Effects

Common side effects of lithium therapy include mild nau-sea or diarrhea, anorexia, fine hand tremor, polydipsia, polyuria, a metallic taste in the mouth, and fatigue or leth-argy. Weight gain and acne are side effects that occur later in lithium therapy; both are distressing for clients. Taking the medication with food may help with nausea, and the use of propranolol often improves the fine tremor. Leth-argy and weight gain are difficult to manage or minimize and frequently lead to noncompliance.

Toxic effects of lithium are severe diarrhea, vomiting, drowsiness, muscle weakness, and lack of coordination. Untreated, these symptoms worsen and can lead to renal failure, coma, and death. When toxic signs occur, the drug should be discontinued immediately. If lithium levels exceed 3.0 mEq/L, dialysis may be indicated.

Side effects of carbamazepine and valproic acid include drowsiness, sedation, dry mouth, and blurred vision. In addition, carbamazepine may cause rashes and orthostatic hypotension, and valproic acid may cause weight gain, alopecia, and hand tremor. Topiramate causes dizziness, sedation, weight loss (rather than gain), and increased incidence of renal calculi (Stahl, 2006).

Client Teaching

For clients taking lithium and the anticonvulsants, moni-toring blood levels periodically is important. The time of the last dose must be accurate so that plasma levels can be checked 12 hours after the last dose has been taken. Tak-ing these medications with meals minimizes nausea. The client should not attempt to drive until dizziness, lethargy, fatigue, or blurred vision has subsided.