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New Treatments for Bipolar Mania

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While the current gold standard for bipolar disorder is lithium, other medications are FDA-approved for the treatment of acute bipolar mania, including valproate and carbamazepine.

Several atypical antipsychotics are also FDA-approved.

Issues with tolerability and adverse effects remain, however. Issues like side effects, weight gain, and sedation make it clear that there is a need to develop more effective medications.

Recent clinical findings suggest that there may be many more options for the treatment of bipolar mania, including:

  • aripiprazole
  • asenapine
  • cariprazine
  • haloperidol
  • olanzapine
  • paliperidone
  • quetiapine
  • risperidone
  • tamoxifen
  • ziprasidone

Another study concluded that antipsychotic drugs were significantly more effective than mood stabilizers for the treatment of acute mania.

  • Olanzapine, risperidone, and quetiapine were more effectively tolerated than haloperidol.
  • Risperidone, haloperidol, and olanzapine were particularly efficacious.

Most of the trials were short (typically 3 weeks), so caution should be taken when applying this information. It is also important to note that because of informed consent and general enrollment issues with manic patients, very severe cases were excluded.

One of the greatest findings in these studies include the tendency for clinicians to treat acute, short term manic episodes with antipsychotics, while long-term mania is treated with mood stabilizers like lithium.

Researchers’ findings also suggested that antidepressants should be stopped throughout manic and mixed episodes.

Improved medications with more pronounced and sustained effects would have an enormous impact on the bipolar community and public health in our society, particularly given the high mortality rates associated with this illness.

A variety of compounds are now being tested that offer different approaches to the treatment of bipolar.

Some of these drugs target pathways specific to lithium, while others focus on other more novel areas, such as NMDA, and opiate receptors.

While the focus of these compounds are specifically for mania, they also may be beneficial during depressive states.

The following are some of these studied compounds for bipolar mania:


Tamoxifen is a protein kinase C (PKC) inhibitor that crosses the blood-brain barrier and is relatively well tolerated in the blood.

Similar to the workings of lithium, tamoxifen enhances the release of dopamine, a neurotransmitter implicated in mania.

A number of studies have shown encouraging results.

The most recent of these was a double-blind study in which tamoxifen was taken along with lithium. The 6-week study showed that in the treatment of acute mania, the tamoxifen along with lithium was more effective than lithium alone.


This selective NDMA glutamate receptor antagonist is approved for the treatment of Alzheimer disease.

Preclinical studies showed that memantine was associated with anti-manic properties, such as the reduction of locomotor hyperactivity.

In studies with bipolar adults, the most reported adverse effects were headache, nausea, and constipation.

Improvements in depression have been noted as well.


Valproic acid is limited in that it is not recommended for women of child-bearing age. Valnoctamide is a variation of this acid.

It is markedly less teratogenic than valproic acid. The drug has anticonvulsant properties similar to valproate and is marked as a sedative in several European countries.

Valnoctamide has been cited in a study as more effective than placebo, but more studies need to be done. However, this may be a medication that women of child-bearing age can use for effective treatment.

The Future

Other treatments are also being studied for the treatment of bipolar mania, and a bright future exists for the treatment of bipolar disorder.

For more information on new treatments for bipolar disorder, continue to visit this blog.

Caution: Remember to always talk to your doctor about your specific treatment plan. 


Photo Credit: Marc Soller via Compfight


Matthews, D. C., Henter, I. D., & Zarate, C. A. (2012). New drug developments for bipolar mania. Psychiatric Times, Retrieved from

New Treatments for Bipolar Mania

Kat Dawkins

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APA Reference
Dawkins, K. (2013). New Treatments for Bipolar Mania. Psych Central. Retrieved on October 1, 2020, from


Last updated: 2 Jun 2013
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