Q. I have bipolar I and ADD (attention deficit disorder). I am no longer able to take any of the current medications for ADD (stimulants, antidepressants) because they have induced mania. Will the recently approved Straterra be appropriate for people with bipolar disorder? How do norepinephrine reuptake inhibitors differ from serotonin reuptake inhibitors in terms of inducing mania?

A. The combination of bipolar disorder (BD) and attention deficit hyperactivity disorder (ADHD) poses challenges for both the patient and the clinician, as you well know. There is certainly the risk that antidepressants or stimulants will cause a switch into mania, or worsen the patient's overall rate of mood cycling.

The medication you refer to--atomoxetine (Straterra)--is not yet available, but may be as early as spring of 2003. (The US Food & Drug Administration is involved in further discussion with the manufacturer and might require additional study). This medication, as you suggest, is a fairly specific norepinephrine reuptake inhibitor, though animal models suggest it may also affect dopamine (as does Ritalin and other stimulants). It is not yet clear how safe atomoxetine will be in bipolar patients, since the pre-release studies have not included known bipolar patients, to my knowledge. Neither do we have good comparative studies of serotonin-reuptake inhibitors versus NE-reuptake inhibitors, in terms of their comparative risk in bipolar disorder.

However, there is at least one case report of atomoxetine (formerly called tomoxetine) setting off a manic bout (Steinberg & Chouinard, Am J Psychiatry. 1985 Dec;142(12):1517-8), and hypomania has been reported with the related NE-reuptake inhibitor, reboxetine (Vieta et al, J Clin Psychiatry 2001 Aug;62(8):655-6).

In the view of most clinicians (including me!), the treatment of bipolar disorder should be prioritized over that of ADHD--bipolar disorder is a much more destructive illness. That said, there is interest in using the agent modafanil [Provigil] in patients with concurrent ADHD and Bipolar Disorder, since it seems not to set off manic/hypomanic episodes. However, this is based on use in a very small number of bipolar subjects! Moreover, Provigil does not have FDA-approved labeling indications for either ADHD or bipolar disorder--it is actually used to treat excessive daytime somnolence in patients with narcolepsy.

There is some limited evidence that modafanil may improve some ADHD symptoms. Interestingly, there is some recent evidence (Dorrego et al, J Neuropsychiatry Clin Neurosci 2002 Summer;14(3):289-95) that lithium may have beneficial effects in some aspects of ADHD--namely, measures of irritability, aggressive outbursts, antisocial behavior, anxiety, and depression. (It's not clear it does much for poor attention per se).

Of course, lithium is quite effective in bipolar disorder. My suggestion is that you discuss these issues not only with your treating psychiatrist, but perhaps also with an expert in ADHD who could consult with your psychiatrist. Then, as always, it's a matter of carefully weighing the risks and benefits of the treatment.

Other Resources:

• More Questions on Bipolar Disorder
• More Questions on ADD/ADHD

April 2003

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