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

Treatment Resistant Treatment Resistant Pediatric BDPediatric BD

Elham Shirazi M.D.

Board of General Psychiatry

Board of Child & Adolescent Psychiatry

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

Factors associated with nonresponse:

1. Misdiagnosis

2. Poor adherence to treatment

3. Comorbid psychiatric and medical conditions

4. Ongoing exposure to negative events (family conflict, abuse)

5. Quality of treatment

Consider whether symptoms persist as a result of:

Inadequate response to treatment

Or as an expected response to inadequate treatment

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)

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)

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 20 mg/day

Quetiapine up to 800 mg/day

Now lack of adequate response after a 4-week trial is a “true” treatment failure.

(Russel E. Scheffer, 2011)

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

For partial or nonresponders to monotherapy:

Combination of 2 mood stabilizers

Or of a mood stabilizer with an atypical antipsychotic is indicated

Medication combinations are additive both in:

Effectiveness

& in side effects

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 most important develpmental, academic, & social milestones.

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.

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

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)

First-line medication for BP depression:

Lamotrigine

Lithium

Valproate

Atypical antipsychotics

For partial or non-responders combine with:

Another atypical antipsychotics

SSRIs

Bupropion

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.

Clozapine:

Is reserved for the most treatment-resistant cases

Because of its side-effect profile.

TMS or augmentation with omega-3 fatty acids are yet to be evaluated for treatment of BP depression in youth.

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.

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 2 mood stabilizers

Or of a mood stabilizer with an atypical antipsychotic is indicated

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)

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)

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)