In children who have a first-degree relative with bipolar disorder, the severity of symptoms predicts whether they will transition to the illness.
The bipolar prodrome refers to children who have a first-degree relative with bipolar disorder, but whose own symptoms don’t cross the threshold for full bipolar. These youth can present with depression, anxiety, inattention, or disruptive behavior, and it’s the severity of the presentation rather than the nature of the symptoms that best predicts their risk of transitioning to full bipolar disorder. Extra caution is needed with these patients, who are prone to worsen with antidepressants and stimulants.
Step 1: Psychotherapy
Psychotherapy, particularly family therapy, has the best evidence in the bipolar prodrome. Therapy is used first in this algorithm, and medications are turned to only if the symptoms impair functioning or impede participation in therapy.
Step 2: Medication
When starting medication, the algorithm splits patients into those with no manic symptoms (unipolar) and those with subsyndromal manic symptoms (bipolar NOS). Antidepressants and stimulants are avoided, or used only with a mood stabilizer, in those with subsyndromal mania or a history of antidepressant induced mania (AIM). Mood symptoms are addressed before treating ADHD or anxiety symptoms. The entire algorithm is detailed in the Table.
The algorithm is part of an ongoing investigation of
as an intervention for youths at risk for bipolar disorder.3 In that context, the goal of medication treatment was to allow participation in therapy by attenuating mood symptoms while minimizing the risk of manic switching. Initial results are promising. In a 2017 study, there were no cases of medication-induced mania in 40 patients with the bipolar prodrome, aged 9 to 17 years, followed for 1 year with the algorithm.2
The study was small and uncontrolled, but its results compare favorably with an earlier investigation of a very different algorithm. In the 1990’s, a small randomized trial tested paroxetine monotherapy vs. valproate + paroxetine in youths with the bipolar prodrome. That study was terminated prematurely due to alarming rates of manic switching and suicidality. Significant mood problems-including mania, suicidality, and hospitalizations-occurred in 75% of those on antidepressant monotherapy vs. 40% of patients on valproate with the antidepressant.4
Refining the algorithm
Dr. Schneck’s algorithm is only a year old, but already new research has added to its steps. Lurisidone, for example, should now be placed first-line among the atypicals, given its recent FDA-approval in pediatric bipolar depression and controlled-trials in unipolar depression with mixed features.5,6
Clonidine could also be added to the list of ADHD options. It is FDA-approved for ADHD, and a handful of pilot studies suggest it has anti-manic properties as well.7 Modafinil and armodafinil also have benefits in both ADHD and bipolar depression.8,9Omega-3 fatty acids deserve a place in the algorithm. Their benefits in prodromal bipolarity are supported by a small study,10 and these low-risk supplements have a moderate effect size in both bipolar and unipolar depression (when the total dose of EPA + DHA is at 1000 mg to 3000 mg and the EPA component is at least 1.5 times the DHA amount).11
The bottom line
The heart of Schneck and colleagues’2 algorithm holds up well to the evidence. Consider these take-home points:
• Proceed cautiously with antidepressants and stimulants in young patients with a strong family history of bipolar disorder
• Antidepressant-induced mania often presents as a mixed state, which feels to the patient like a worsening of their depression, so take seriously any signs of worsened mood on these agents
• If manic symptoms are present, attend to them with a mood stabilizer before starting treatments that can further destabilize mood
• Stabilize the environment as well, with family therapy, skill building, and regulation of sleep and circadian rhythms.
Dr. Aiken is the Director of the Mood Treatment Center, Editor in Chief of The Carlat Psychiatry Report, and Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine. He does not accept honoraria from pharmaceutical companies but he but receives honoraria from W.W. Norton & Co. for Bipolar, Not So Much, a book he coauthored with Jim Phelps, MD.
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3. Miklowitz DJ, Schneck CD, Walshaw PD, Garrett AS, Singh MK, Sugar CA, and Chang KD. Early intervention for youth at high risk for bipolar disorder: a multi-site, randomized trial of family focused treatment.Early Interv Psychiatry. 2017;0:1-9.
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