Evidence-Based Reviews

How to reduce mania risk when prescribing stimulants

Current Psychiatry. 2005 October;4(10):36-54

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Carbamazepine can be effective, but it makes some youths aggressive or disorganized. Antipsychotics have not been tested in controlled trials in bipolar children and are not considered first-line treatments, especially as mood stabilizers. They can be effective for childhood mania, but outpatients needing ADHD treatment usually do not have severe manic syndromes.

Algorithm Reducing mania risk: Using stimulants in children with bipolar disorder

Combination therapy. Like many adults, bipolar children often require combinations of mood stabilizers. Kowatch et al³⁶ found that 16 of 20 acutely ill bipolar children (mean age 11) responded to a combination of mood stabilizers after not responding to 8 weeks of a single mood stabilizer. Because bipolar disorder with comorbid ADHD suggests a complex pathophysiology, patients with both disorders may be more likely to require mood-stabilizer combinations than those with bipolar disorder alone.

The goal in treating bipolar disorder is to eliminate symptoms as completely as possible. In bipolar children with comorbid ADHD, be certain that subtle hypomanic symptoms—irritability, decreased sleep, hypersensitivity to interactions, psychosis—have remitted, as they could account for continued inattention. Persistent mood lability may indicate incomplete treatment of the mood disorder, which can increase sensitivity to destabilization by a stimulant.

If a child remains inattentive after the mood disorder is controlled, consider whether medications for the mood disorder are to blame. If medications are working well but causing cognitive side effects, a cholinesterase inhibitor may help.

Adding stimulants. If attention problems persist, consider cautiously adding a stimulant. Informed consent includes telling patients and families about the risks of mood destabilization with stimulants, even when used with mood stabilizers.

Increase stimulant dosage very slowly, and monitor the patient closely for emerging mood instability or subtle evidence of dysphoric hypomania. Address hypersensitivity to sounds, increased irritability, or other signs of activation with more-aggressive mood stabilization before assuming that these are ADHD symptoms that require a higher stimulant dosage.

Sustained-release stimulant preparations are probably second-line choices in patients with concomitant bipolar disorder. With long-acting stimulants, any worsening of the mood disorder will take longer to wear off. Antidepressants such as bupropion are potential alternatives to stimulants but are as likely to induce hypomania and mood cycling and may not be as effective.

Compared with stimulants, atomoxetine has a less-potent antidepressant effect and may be somewhat safer, but it is not as effective for ADHD and is longer-acting. Thus, atomoxetine could be a first-line alternative for comorbid ADHD, with stimulants being added if it is not effective. Clonidine can reduce hyperactivity but does not stabilize mood or improve attention.

When an antidepressant has brought bipolar depression into remission, discontinue it slowly to reduce the risk of rebound while continuing mood stabilizers to prevent recurrence. Because ADHD is not cyclical like bipolar depression, inattention returns for many patients when stimulants are withdrawn.

We do not yet know whether the risk of mood destabilization increases with long-term stimulant use, but discontinuation-induced refractoriness has not been reported with stimulants as it has with mood stabilizers and antidepressants. Thus, trying to withdraw stimulants once ADHD symptoms have remitted is prudent, while supplementing the regimen with behavioral treatments. If managing ADHD symptoms requires continued stimulant treatment, monitor the patient closely for mood destabilization.

Related resources

American Academy of Child and Adolescent Psychiatry. Facts for families: Bipolar disorder in children and teens.
www.aacap.org/publications/factsFam/bipolar.htm.
National Institute of Mental Health. Database on ADHD.
www.nimh.nih.gov/publicat/adhd.cfm.

Drug brand names

Amphetamine salts • Adderall
Atomoxetine • Strattera
Bupropion • Wellbutrin
Carbamazepine • Tegretol, others
Clonidine • Catapres
Dexmethylphenidate • Focalin
Fluoxetine • Prozac
Lithium • Lithobid, others
Methylphenidate • Concerta,
Ritalin, others
Valproate • Depakene, Depakote
Venlafaxine • Effexor

Disclosures

Dr. Dubovsky receives research support from UCB Pharma, Forest Laboratories, and Solvay Pharmaceuticals, and is a speaker for Janssen Pharmaceutica and Forest Laboratories.