Antidepressants/antidepressant therapy switch” effect

Lamotrigine is effective for the maintenance treatment of bipolar I disorder in adults. It has both antidepressant and mood-stabilizing effects, and it may have augmenting properties when combined with lithium or valproate. It has low rates of switching patients to mania. Although it is less effective for acute mania compared to lithium and valproate, it may be beneficial for the maintenance therapy of treatment-resistant bipolar I and II disorders, rapidcycling, and mixed states. It is often used for bipolar II patients. 

There is, however, a unique risk in the bipolar form that antidepressant treatment may trigger a switch into mania. This may occur either as the natural outcome of recovery from depression or as a pharmacological effect of the drug. Particular antidepressants (the selective serotonin reuptake inhibitors) seem less liable to induce the switch into mania than other antidepressants or electroconvulsive therapy. Treatment for mania consists initially of antipsychotic medication, for instance the widely used haloperidol, often combined with other less specific sedative medication such as the benzodiazepines (lorazepam intramuscularly or diazepam orally). The manic state will usually begin to subside within hours and this improvement develops further over the next 2 weeks. If the patient remains disturbed with manic symptoms, additional treatment with a mood stabilizer may help. 

During the maintenance phase, treatment can be fine-tnned. If persistent side effects (especially EPS) are a problem, then the antipsychotic can be gradnally switched or conntermeasures snch as anticholinergic therapy can be taken. In addition, maintenance therapy is also an appropriate time to address the less dramatic bnt nonetheless tronblesome symptoms snch as a mood distnrbance. Antidepressants are often used to treat depressed mood in patients with schizophrenia. Likewise, benzodiazepines are commonly nsed with an antipsychotic to treat persistent yet subsyndromal anxiety in schizophrenia patients. 

Paradoxically, ECT is equally useful in both the acute manic and depressive phases of bipolar disorder, constituting the only truly bimodal therapy presently available. For example, in their literature review, Mukherjee et al. ( 51) found that ECT was associated with marked clinical improvement or remission in 80% of patients undergoing treatment for an acute manic episode. This is not the case for lithium, valproate, or CBZ, which, at best, have relatively weak acute antidepressant effects. Drug therapies may also induce a switch from a depressed to a manic phase, whereas ECT can control both phases of the illness. 

These drugs are well absorbed on oral administration, but antidepressant effects require 2 to 4 weeks of treatment. Enzyme regeneration, when irreversibly inactivated, varies but usually occurs several weeks after termination of the drug. Thus, when switching antidepressant agents, a minimum of 2 weeks delay must be allowed after termination of MAO-inhibitor therapy. MAO inhibitors are metabolized and excreted rapidly in the urine. 

To avoid drug toxicity and prevent the precipitation of serotonin syndrome, duration cf effect should be considered when switching between antidepressants (e.g., a MAO inhibitor should not be started for 5 weeks after discontinuing fluoxetine 2-3 weeks should elapse between stopping a nonselective MAO inhibitor and initiating therapy with a tricyclic antidepressant). 

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