In 2013 the International Society for Bipolar Disorders and the Canadian Network for Mood and Anxiety Treatments combed through the scientific literature and put together these guidelines for the pharmacological treatment of bipolar disorder. Treatments are classified as 1st, 2nd, or 3rd line based on the strength of existing evidence to support their effectiveness. The guidelines also mention treatments that are sometimes used in bipolar disorder but, for whatever reason, don’t necessarily have a research base to back them up.
No treatment guideline in the world is going to be able to say what treatment is going to work for a specific individual. However, they can provide a good idea of what has the best chance of working, and I think it’s always valuable to know what your options are.
Here are the recommendations for acute mania, acute depression, and maintenance treatment.
Acute mania
1st line:
- lithium
- divalproex
- atypical antipsychotic: risperidone, paliperidone, olanzapine, quetiapine, aripiprazole, ziprasidone, asenapine
2nd line:
- carbamazepine (mood stabilizer)
- haloperidol (typical antipsychotic)
Not supported by evidence:
- gabapentin
- lamotrigine
- topiramate
Acute bipolar I depression
1st line:
- lithium
- lamotrigine
- quetiapine
- lithium/divalproex + selective serotonin reuptake inhibitor (SSRI) or bupropion
- olanzapine + SSRI
- lithium + divalproex
2nd line:
- divalproex
- lurasidone (an atypical antipsychotic)
- quetiapine + SSRI
- modafinil (stimulant)
- lithium/divalproex + lamotrigine or lurasidone
3rd line:
- carbamazepine
- olanzapine as monotherapy (i.e. the only treatment)
- electroconvulsive therapy (ECT)
- lithium combined with carbamazepine, pramipexole, or an MAOI antidepressant
- lithium/divalproex + venlafaxine or tricyclic antidepressant
- lithium/divalproex/carbamazepine + SSRI + lamotrigine
- quetiapine + lamotrigine
Not supported by evidence:
- gabapentin
- aripiprazole
- ziprasidone
Acute bipolar II depression
1st line:
- quetiapine
2nd line:
- lithium
- lamotrigine
- divalproex
- lithium/divalproex + antidepressant
- lithium + divalproex
- atypical antipsychotic + antidepressant
3rd line:
- antidepressant monotherapy
- quetiapine + lamotrigine
- ECT
- N -acetyl cysteine
- T3 form of thyroid hormone
Maintenance therapy
1st line:
- lithium
- lamotrigine
- divalproex
- atypical antipsychotics: olanzapine, quetiapine, risperidone, aripiprazole
- lithium/divalproex + quetiapine/risperidone/aripiprazole/ziprasidone
2nd line:
- carbamazepine
- paliperidone
- lithium + divalproex/carbamazepine
- lithium/divalproex + olanzapine
- lithium + risperidone or lamotrigine
- olanzapine + fluoxetine
3rd line:
- asenapine
- phenytoin
- clozapine
- ECT
- topiramate
- omega-3 fatty acids
- oxcarbazepine, gabapentin
Not supported by evidence:
- gabapentin, topiramate, or antidepressants when used alone as monotherapy
- flupenthixol as an adjunctive treatment
The role of antidepressants
Antidepressants don’t always work well in bipolar disorder, and they can potentially do more harm than good. In case you’re interested, the International Society for Bipolar Disorder has a task force report on the use of antidepressants in bipolar disorder. Here’s a quick overview of their findings.
Do short-term antidepressants work for bipolar depression?
There’s evidence to support a few specific options: fluoxetine in combination with quetiapine, and paroxetine or bupropion added to a mood stabilizer.
Can antidepressants be used for long-term maintenance for bipolar?
There isn’t good evidence to support this being effective.
Can antidepressants on their own be used for bipolar depression?
The evidence does not support the use of antidepressant monotherapy for bipolar I depression. The picture is somewhat more optimistic in bipolar II, but still, the quality of evidence is weak.
Should antidepressants be used in bipolar mixed states?
The evidence doesn’t support this.
When is are antidepressants most likely to cause a manic switch?
A manic switch as a result of antidepressants is more likely (and more likely to be severe) in bipolar I. Tricyclic antidepressants, mirtazapine, and possibly SNRIs (e.g. venlafaxine) may be more likely to trigger a manic switch than other antidepressants.
And there you have it, folks. Was there anything in the guidelines that surprised you? And for those of you who have bipolar disorder, how does your treatment regimen compare to what’s in the guidelines?
For more posts on psychiatric medications, visit the Psych Meds Made Simple page. There’s also a Psych Meds 101 series covering:
Reference
Yatham, L.N., et al. (2013). Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: Update 2013. Bipolar Disorders, 15, 1-44.
There’s also a Patient & Family Guide to the CANMAT guidelines.
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Ashley L. Peterson
BScPharm BSN MPN
Ashley is a former mental health nurse and pharmacist and the author of four books.