Glutamatergic modulators

What are glutamatergic modulators for bipolar disorder?

Glutamate receptor modulators, such as ketamine and memantine, have been suggested as potential treatments for bipolar disorder when there are sub-optimal responses to other pharmaceuticals. Currently approved treatments for bipolar depression (i.e. several mood stabilisers, antidepressants and antipsychotics) are thought to involve a number of different neurotransmitters such as serotonin, dopamine, and norepinephrine. There is emerging evidence that glutamatergic system dysfunction may also play an important role in the pathophysiology of bipolar depression, and that drugs targeting the NMDA (N-methyl-D-aspartate) glutamate receptor may have antidepressant effects.

What is the evidence for glutamatergic modulators?

Moderate quality evidence finds a medium-sized improvement in depression symptoms with N-acetylcysteine compared to placebo. Most studies reported no differences in adverse events. The result for depression was not consistently found across reviews due to differences in the included studies.

Moderate to high quality evidence finds no benefit of adjunctive memantine for depression or mania symptoms.
Only low quality evidence was found for adjunctive ketamine, with review authors suggesting it has the potential to have a rapid and transient antidepressant effect, although the efficacy of a single intravenous dose may be limited.

November 2021

Image: ©Sergey Tarasov –

Last updated at: 4:41 pm, 29th November 2021
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