Fluoxetine is the only antidepressant to be used in bipolar disorder, NICE says

NICE is now focusing on the effectiveness of individual drugs, rather than the tradition of recommending drug classes as a whole for its bipolar guidance.

Antidepressants are not effective at treating bipolar depression, except for one, fluoxetine, and only in combination with the atypical antipsychotic olanzapine

Fluoxetine is the only antidepressant that is effective in treating bipolar depression, and only in combination with the atypical antipsychotic olanzapine, says an updated clinical guideline[1]
 published by the National Institute for Health and Care Excellence (NICE) on 24 September 2014.

This marks a change from NICE’s 2006 bipolar guideline, which did not specify any particular drug, but recommended that a drug from the antidepressant and antimanic drug classes should be used in combination to treat bipolar depression.

The updated guideline also recommends specific antipsychotics for the manic episodes of the disorder, no longer recommending the drug class as a whole.

“NICE is now focusing on the effectiveness of individual drugs, rather than the tradition of recommending drug classes as a whole,” says Richard Morriss, professor of psychiatry and mental health at the University Of Nottingham who led the development of the guideline.

The evidence base around the use of antidepressants has almost doubled since the previous guideline was published, he says. “Bipolar depression looks a lot like unipolar depression, so the assumption was that treatment should be the same. But now we have gone from only having a weak evidence base to having evidence with statistical significance,” Morriss says.

“It confirms that antidepressants should not be used alone and also that these drugs are not effective for bipolar depression, which needs to be treated in a distinct way,” he adds. Monotherapy with antidepressants or lithium is no better than placebo, states the NICE guideline.

The new recommendations are more specific, focus on recovery and take into account the “whole package” of care, according to Morriss.

Bipolar disorder has an estimated lifetime prevalence of 1–2% in the UK. The disorder is characterised by cycles of mania and depression with complete or incomplete recovery in between. Medication used to treat the condition varies depending on which part of the disease cycle the patient is in and whether they are already taking medication for the condition.

For bipolar depression, the recommended first-line treatments are fluoxetine with olanzapine, or monotherapy with another atypical antipsychotic, quetiapine. Olanzapine or lamotrigine monotherapy can also be considered, says NICE.

For mania, the antipsychotics risperidone, haloperidol, olanzapine and quetiapine are recommended. After symptoms resolve, these drugs should be continued for another four weeks at which point long-term drug treatment options should be considered.

Lithium continues to be the go-to drug for the long-term management of bipolar disorder, because it still has the best evidence base, says Morriss. Olanzapine, quetiapine and valproate are recommended as second-line treatments if there is no response or only a partial response to lithium.

The guideline states the importance of non-pharmacological therapy, such as psychological treatments, including cognitive behavioural therapy. Psychological therapy could be used on its own for milder cases of bipolar depression, adds Morriss.

Psychological interventions form the cornerstone of therapy for adolescents and children in the new guideline as bipolar drug treatments can have a damaging effect on children’s growth and development. But when medicines are needed, the treatment options are largely the same as for adults, with the addition of aripiprazole for mania, based on a positive technology appraisal by NICE in 2013.

As part of focusing on the whole package of care, Morriss also emphasises the use of personal care plans. “Patients on maintenance treatment can be given a small volume of standby medication in case they begin to experience the symptoms of mania or depression,” says Morriss. “The pharmacist will need to play a key role in helping the patient understand when to take these medications.”


[1] Bipolar disorder: the assessment and management of bipolar disorder in adults, children and young people in primary and secondary care. The National Institute for Health and Care Excellence. NICE clinical guideline 185: 2014.

Last updated
The Pharmaceutical Journal, PJ, 11 October 2014, Vol 293, No 7831;293(7831):DOI:10.1211/PJ.2014.20066690

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