Antidepressant Switching

The options include increasing the dose of the current antidepressant, switching antidepressants, or the addition of an augmenting agent. This decision should account for the current dose of medication, the degree of partial response if any, and the patient s preferences. 

Take extra care with antidepressant switching. 

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. 

Treatment of depressive episodes in bipolar disorder patients presents a particular challenge because of the risk of a pharmacologic mood switch to mania, although there is not complete agreement about such risk. Treatment guidelines suggest lithium or lamotrigine as first-line therapy.17,41 Olanzapine has also demonstrated efficacy in treatment of bipolar depression, and quetiapine is under review for approval of treatment of bipolar depression.42 When these fail, efficacy data support use of antidepressants. 

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. 

Switching non-responsive patients from an SSRI to an SNRI led 25 per cent of them to get better. Change from an SSRI to bupropion produced virtually the same remission rate (26 per cent). But what of the patients who were not switched to a different class of antidepressant, but instead were simply given another SSRI Twenty-seven per cent of these patients also got better - a remission rate that is virtually identical to that produced by changing to a different type of medication. In other words, the rate of improvement did not depend on the kind of drug to which the patient had been switched. Simply changing from one SSRI to another was as effective as changing to a completely... 

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. 

The STAR D study showed that one in three depressed patients who previously did not achieve remission with an antidepressant became symptom-free with the help of an additional medication (e.g., bupropion sustained release), and one in four achieved remission after switching to a different antidepressant (e.g., venlafaxine XR). 

Infrequently, SSRIs produce dystonic reactions, which are intense mnscle spasms nsnally of the face and neck. They may cause akathisia, a restless inability to sit still. Dystonic reactions and akathisia are more commonly side effects of the dopamine-blocking antipsychotics. It is believed that SSRIs prodnce these effects because increasing 5HT activity tends to decrease dopamine. When these side effects occur, the SSRI should be switched to another antidepressant. 

Switching antidepressants is usually straightforward. Often, the first medication is decreased as the new one is started and gradually increased such that there is an overlap between the two. 

When switching between a MAOl and other antidepressants that affects serotonin activity, the first medication must be allowed to wash out of the patient s system before the new antidepressant is started. The duration of this washout period is determined by the half-life of the antidepressant that is being discontinued. If a washout is neglected, then a potentially dangerous serotonin syndrome may result. 

In addition, whenever an antidepressant that blocks serotonin reuptake is discontinued, an unpleasant but harmless discontinuation syndrome manifested by abdominal discomfort, instability, anxiety, and occasionally painful shock-like sensations in the extremities can arise. The risk appears to be greatest with venlafaxine and paroxetine. Consequently, switching from one of these medications to another that does not block serotonin reuptake requires a gradual taper of the first medication over days to weeks. 

More controversial is the occurrence of antidepressant-induced mania or hypo-mania. DSM-IV specifically states that manic or hypomanic episodes triggered by antidepressant treatment should not count toward the diagnosis of BPAD. However, clinicians have traditionally viewed antidepressant-induced switching from depression into mania as an unmasking of a preexisting BPAD that had previously been unrecognized and undiagnosed. 

The chief concern when using antidepressants in treating bipolar depression is to avoid switching the patient into a manic episode. Although any antidepressant can theoretically precipitate a manic episode in a susceptible patient, the tricyclic... 

It appears that SSRls and bnpropion are less likely than TCAs to indnce mania. Venlafaxine, perhaps becanse of its dnal effects on serotonin and norepinephrine like the TCAs, also appears to increase the likelihood of switching into mania. Rarely, if ever, shonld an antidepressant be nsed in bipolar patients withont concomitant treatment with a mood stabilizer. 

Labbate LA, Croft HA, Olehansky MA. Antidepressant-related erectile dysfnnction management via avoidance, switching antidepressants, antidotes, and adaptation. J Clin Psychiatry 2003 64(Supplement 10) 11-19. 

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. 

Generalized Sociai Anxiety Disorder, Treatment Resistance. A significant minority of patients will not experience a satisfactory treatment response to antidepressant therapy, even after a trial of adequate duration at full strength doses. For those with comorbid depression who are experiencing no benefit from SSRI treatment for either the anxiety or depression, then switching treatment is advisable. The options include switching to another SSRI, a SNRI (venlafaxine or perhaps dulox-etine), or, when other alternatives fail, phenelzine. 

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