Stabilizing Drugs

Frequently monitor the patient for signs of drug toxicity and seizures until the patient s drug concentrations have stabilized. Drug interactions are likely when patients are on more than one AED therefore, closely evaluate the patient s entire medication profile, and change medications or doses to minimize the interaction, if possible. 

Pharmacotherapy is the cornerstone of acute and maintenance treatment of bipolar disorder. Mood-stabilizing drugs are the usual first-choice treatments and include lithium, divalproex, carbamazepine, and lamotrigine. Atypical antipsychotics other than clozapine are also approved for treatment of acute mania. Lithium, lamotrigine, olanzapine, and aripiprazole are approved for maintenance therapy. Drugs used with less research support and without Food and Drug Administration (FDA) approval include topiramate and oxcarbazepine. Benzodiazepines are used adjunctively for mania. 

Mood-stabilizing drugs are considered the primary pharmacotherapy for relapse prevention. Olanzapine and aripiprazole are also approved for maintenance therapy. 

Increasing evidence shows an effect of lithium on suicidal behavior that is superior to other mood-stabilizing drugs.28 Lithium reduces the risk of deliberate self-harm or suicide by about 70%. 

It is common for lithium to be combined with other mood-stabilizing drugs or antipsychotic drugs, if necessary, in order to achieve more complete remission of symptoms. Studies indicate that monotherapy is often insufficient to reach this goal.17... 

Lithium and other mood-stabilizing drugs require baseline and routine laboratory monitoring to help determine medical appropriateness for initiation of therapy and monitoring of potential adverse effects. Guidelines for such monitoring are outlined in Table 36-6. 

Mechanism of Action The mechanism of action of carbamazepine is not well understood. It blocks ion channels and inhibits sustained repetitive neuronal excitation, but whether this explains its effect as a mood-stabilizing drug is not known.32... 

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... 

Guidelines agree that when antidepressants must be used, they should be combined with a mood-stabilizing drug to reduce the risk of mood switch to hypomania or mania.17,41 The question of which antidepressant drugs are less likely to cause a mood switch is not resolved. Anecdotal reports suggested bupropion may be less likely to cause this effect, but systematic reviews have not supported this conclusion. Prevailing evidence recommends that tricyclic antidepressants be avoided.41,43... 

Duration of antidepressant therapy is also an unsettled question. It may be possible in some patients to prevent depressive relapse with a mood-stabilizing drug without maintenance antidepressant therapy following acute treatment with an antidepressant. If so, the risk of a mood switch with continued antidepressant therapy would be reduced. 

A nonaqueous solvent or a mixed aqueous/nonaqu-eous solvent system may be necessary to stabilize drugs, such as the barbiturates, that are readily hydrolyzed by water, or to improve solubility (e.g., di-gitoxin). Nonaqueous solvents must be carefully screened and tested to ensure that they exhibit no pharmacological action, are nontoxic and nonirritating, and are compatible and stable with all ingredients of a formulation. 

Intrinsic reinforcement. Reinforcement that comes from inside the person. Mood stabilizers. Drugs that treat disorders with mood cycles, such as Bipolar Disorder. 

In CONCLUSION, lithium is universally accepted as a mood-stabilizing drug and an effective antimanic agent whose value is limited by its poor therapeutic index (i.e. its therapeutic to toxicity ratio). Neuroleptics are effective in attenuating the symptoms of acute mania but they too have serious adverse side effects. High potency typical neuroleptics appear to increase the likelihood of tardive dyskinesia. Of the less well-established treatments, carbamazepine would appear to have a role, particularly in the more advanced stages of the illness when lithium is less effective. 

Williams RS, Cheng L, Mudge AW, Harwood AJ 2002 A common mechanism of action for three mood-stabilizing drugs. Nature 417 292-295... 

Class I— membrane stabilizing drugs to reduce cardiac electrical excitability molecules that are sodium channel blockers, usually based on local anesthetic molecular structure... 

LITHIUM, MOOD-STABILIZING DRUGS, AND OTHER TREATMENT FOR BIPOLAR DISORDER... 

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. 

---