Treatment Resistant Pediatric BD

1. Treatment Resistant Pediatric BD Elham Shirazi M.D. Board of General Psychiatry Board of Child & Adolescent Psychiatry

2. Pediatric BD: • Less adequate treatment response • More prolonged & treatment-refractory course • More relapse rates • More recurrent & intractable • More episodes over the course of a year • Reduced interepisode recovery

3. Factors associated with nonresponse: • Misdiagnosis • Poor adherence to treatment • Comorbid psychiatric and medical conditions • Ongoing exposure to negative events(family conflict, abuse) • Quality of treatment

4. Consider whether symptoms persist as a result of: • Inadequate response to treatment • Or as an expected response to inadequate treatment

5. Step 1 Discontinue potentially destabilizing agents: • Antidepressants • Can promote mania, mixed states, or rapid cycling in children/ adolescents with BD • Can increase the frequency & severity of mood symptoms (Russel E. Scheffer, 2011)

6. Stimulants • Can be problematic in patients at risk for BD disorder. • Try to discontinue stimulants while stabilizing patients’ mood symptoms • Once the patient’s mood symptoms are controlled on a mood stabilizer regimen • Using stimulants for comorbid ADHD did not affect relapse rate (Russel E. Scheffer, 2011)

7. Step 2 Optimize the antimanic agents the patient is currently receiving: • Serum Li levels between 0.8–1.2 mEq/dl • VPA levels between 80–120 mEq/dl • Risperidone up to 4 mg/day • Olanzapine up to 20mg/day • Quetiapine up to 800 mg/day • Now lack of adequate response after a 4-weektrial is a “true” treatment failure. (Russel E. Scheffer, 2011)

8. If there is no improvement on a treatment after several months, don’t continue that treatment • Use combinations other than the one that hasn’t worked

9. For partial or nonresponders to monotherapy: • Combination of 2mood stabilizers • Or of a mood stabilizer with an atypicalantipsychotic is indicated Medication combinations are additive both in: • Effectiveness • & in side effects

10. If remission is achieved on a particular regimen, it should be continued as long as possible • At least until the child/adolescent has navigated his mostimportant develpmental, academic, & social milestones.

11. Majority of subjects relapse after the switch to monotherapy • A child stabilized on 2 medications needs to be maintained as such since the relapse rate on one drug is high. • Even in most treatment responsive youth with PBD, it is common to need 2 mood stabilizers • Lithium alone has not been successful in this age group as a maintenance medication.

12. BD + ADHD? In cases where clinicians can not decide between mania & ADHD: • If the child becomes more irritable or aggressive with ADHD treatment • Use an atypical antipsychotic or a mood stabilizer • Followed by retrying the ADHD treatment

13. Keep in mind that “rebound” the apparent return of worse ADHD symptoms at the end of the day • Has no diagnostic implications • & sometimes subsides over time (Carlson 2003)

14. First-line medication for BP depression: • Lamotrigine • Lithium • Valproate • Atypical antipsychotics

15. For partial or non-responders combine with: • Another atypical antipsychotics • SSRIs • Bupropion

16. DMDD + ADHD + ODD • Comorbid DBD predict a poorer response to treatment. (Masi 2004, State 2004) • A treatment algorithm for ADHD & aggression might be a reasonable course of action (Carlson 2007) • Antimanic medications have efficacy as antiaggression medication.

17. Clozapine: • Is reserved for the most treatment-resistant cases • Because of its side-effect profile. • TMSor augmentation with omega-3 fatty acids are yet to be evaluated for treatment of BP depression in youth.

18. ECT: • May be indicated for adolescents with severe & most treatment resistant disorders Considered for adolescents with well-characterized BDI who have: • Severe episodes of mania or depression • Are nonresponsive • Or unable to take standard medication therapies.

22. For subjects who do not respond to the initial monotherapy: • Treat with one of the other mood stabilizers • Or an atypical antipsychotic not previously tried For subjects with a partial response to monotherapy: • Combination of 2mood stabilizers • Or of a mood stabilizer with an atypicalantipsychotic is indicated

23. Even in most treatment responsive youth with PBD, it is common to need 2 mood stabilizers • & a stimulant to treat ADHD symptoms. • The clinical course of PBD includes many affective & behavioral bumps. • If you attempt to treat all of these bumps it results in excessive polypharmacy. (Russel E. Scheffer, 2011)

24. Also discontinue GABA-ergic agents • Gabapentin, Tiagabine, Levetiracetam, Pregabalin • GABA-ergic agents frequently cause disinhibition in children • Are not effective in treating manic symptoms (Russel E. Scheffer, 2011)

25. Step 3 • Use a limited number of mood stabilizers (one or two) • Nonconventional & empirically unsupported medications (e.g., oxcarbazepine) are discontinued • & replaced with a first-line treatment agent (e.g., Li, VPA, risperidone, olanzapine, or quetiapine) (Russel E. Scheffer, 2011)