Treating Bipolar Depression in Youth

August 29, 2012 · Posted in Potential Treatments 

depressed boyAt the Ryan Licht Sang pediatric bipolar conference in March, researcher Karen Dineen Wagner summarized the controlled data on treatment of bipolar depression in children. Almost no data exist, with the exception of one study in which quetiapine (Seroquel) was not found to be more effective than placebo.

Unlike mania, for which there are several approved treatments for children aged 10 to 17, there are no FDA-approved treatments for bipolar depression in children.

In adults, quetiapine is the only approved monotherapy for bipolar depression, and the only other approved treatment is the combination of fluoxetine and olanzapine. Despite the frequency with which conventional antidepressants (SSRIs, SNRIs, bupropion, and tricyclic antidepressants) are prescribed for bipolar depression, the data on their efficacy is mostly negative, based on a 2010 meta-analysis by researchers Sidor and MacQueen.

Given that there is little data available even for adults, Wagner reviewed the open (uncontrolled) studies on depression in children with bipolar disorder. Some evidence of good response to lithium or lamotrigine can be found in case series and chart reviews. In studies of atypical antipsychotics for mania in children, the mania rating scales used contain items about depression, and these often show some improvement.

Wagner concluded that one option is to use monotherapy with atypicals, lithium, or lamotrigine in children with bipolar depression.

Wagner created a revised Mood Disorder Questionnaire for Adolescents (MDQ-A), which focuses on a possible diagnosis of bipolar disorder instead of unipolar depression. This was published in the Journal of Clinical Psychiatry in 2006 and we have reproduced it here. Dr. Wagner indicated that the instrument is more valid when the answers are supplied by a parent than by the adolescent.

Editor’s Note: The lack of research on the treatment of children with bipolar disorder is a public health problem. 

Factors Making the Lack of Good Data Troublesome

  1. Epidemiological data published by Merikangas et al. in 2010 indicate that 2.7% of children and adolescents in the US have bipolar disorder. The illness began with a depressive episode in at least half of those children. This means we lack good information for the treatment of more than a million children in the US.
  2. Depression is associated with considerable dysfunction and disability.
  3. Roughly two-thirds of the weeks of follow up after an episode of mania in children are associated with symptomatic depression or mania.
  4. Depression is a major cause of suicide, and suicide rates have increased in recent studies of adolescents.
  5. Among adults in the Bipolar Collaborative Network (wherethis editor is an investigator) and in the STEP-BD study, onset of illness in childhood was associated with a poorer outcome in adulthood.
  6. Duration of time from illness onset to first treatment of depression or mania is an independent risk factor for a poor outcome in adulthood, resulting in more time depressed and greater severity of depression, more episodes, and less time euthymic.

Given these immediate and long-term problems related to childhood onset bipolar depression and the relative absence of good data on treatment (from randomized, double-blind, placebo-controlled clinical trials), how should parents, physicians, and clinicians proceed? A number of important principles may form useful guidelines.

Guidelines for Treating BP Depression in Youth

  1. Engage the child and family in treatment, since not treating this illness will likely convey serious harm.
  2. Use the safest and best tolerated treatments first.
  3. Since there are no FDA-approved treatments for bipolar depression in childhood, use non-FDA-approved treatments.
  4. Accurate diagnosis and longitudinal follow up are essential.
  5. Careful monitoring and follow up will facilitate evaluation of the treatments undertaken and allow the development of optimal approaches for a given child.
  6. Educate families about the illness, giving honest information about the current paucity of controlled studies and gaining informed consent.
  7. Encourage family education and therapy. This can include:
    a. Family psychoeducation about illness recognition and management.
    b. The family focused treatment pioneered by David Miklowitz.
    c. The multi-family psychoeducational psychotherapy developed by Mary Fristad.
    d. Cognitive behavioral therapy (CBT), dialectical behavior therapy (DBT), and Interpersonal and Social Rhythm Therapy (IPSRT) for older children and adolescents.
  8. Parents, with the help of their own physicians, should optimize their own treatment (if they have an affective illness) and/or look after their own wellbeing with as much support as they can acquire from family, friends, and social and advocacy groups.
  9. Recognize that many potential psychopharmacological options are available, though current recommendations and treatment sequences may change dramatically as more information becomes available.

Accordingly, clinicians and parents should view the following ideas from this editor as highly preliminary. Please remember that BNN editors cannot take medical responsibility for any preliminary ideas, strategies, suggestions, and direct or implied recommendations published here, which must be affirmed and authorized by the appropriate treating physician who bears the medical responsibility for any treatments undertaken and who must assess treatments by reviewing the available literature as it evolves and the child’s progress. The preliminary and perhaps idiosyncratic views of the editor cannot be taken as recommendations for any given individual, as the application of these views to a given individual in the absence of a detailed review of their history and condition may be entirely inappropriate.

Possible Treatment Options for Bipolar Depression in Children and Adolescents in Absence of Good Evidence-Based Data

(To be reviewed and revised as new information becomes available)

If my child were depressed after an episode of mania (i.e. had bipolar depression), I would consider doing some of the following:

  1. Get good education about the illness and monitor the child’s mood and behavior on the daily prospective Life Chart (NIMH-LCM). This is available on our website,
  2. Get the child evaluated by an expert and begin some form of psychotherapy for them and for the family.
  3. Encourage a good diet and as much exercise as possible.
  4. Include in the diet omega-3 fatty acids, which may have some antidepressant efficacy and are probably good for him/her anyway.
  5. Check for low Vitamin D levels and treat accordingly.
  6. Consider N-acetylcysteine (NAC), which has been found to have antidepressant effects in adults and anti-irritability effects in children aged 8 to 17 with autism.
  7. Consider NAC more strongly if the patient begins to experiment with alcohol or marijuana, as NAC may help with substance avoidance.
  8. Avoid the usual antidepressants for unipolar depression, since early age of onset of depression is a risk factor for switching into mania after taking antidepressants. Kiki Chang of Stanford University and Joe Biederman of Massachusetts General Hospital have reported that they see lots of activation and/or switching in children with bipolar disorder treated with antidepressants.
  9. Consider starting lamotrigine at very low doses (12.5mg/day with very slow upward titration to limit the risks of serious rash, which occurs in 1/5000 adults and about 1/2500 children).
  10. Consider folic acid (folate), which can potentiate effects of antidepressants. There is some evidence that lamotrigine can interfere with folate metabolism.
  11. If needed, add an atypical antipsychotic with low weight gain potential, such as the partial dopamine agonist aripiprazole (Abilify, starting at 1mg/day or lower) or lurasidone (Latuda). There are two instances of positive data on lurasidone in adult bipolar depression, and the drug has a good profile of weight and metabolic neutrality so far in adults. Or consider quetiapine (Seroquel), especially if anxiety and insomnia are present (although a trial in children and adolescents with bipolar depression was not positive).
  12. If needed, augment treatment of an older child with lithium.
  13. If the child is still depressed, add very, very short-term treatment with minute doses of a selective serotonin reuptake inhibitor (SSRI) or bupropion under the cover of one or more mood stabilizers above.
  14. If the child is still depressed, consider a trial of repetitive transcranial magnetic stimulation (rTMS), the effectiveness of which in adolescents has been reported by Chris Wall at the Mayo Clinic.



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