How Bipolar Medications Work

Lithium

Lithium has been the gold standard of bipolar medication since the 1950’s. However, lithium only works in approximately one third of patients. The side effects can be severe and include nausea, weight gain, muscle tremors, emotional numbing, weight gain and birth defects for the offspring of pregnant women. Up until recently, scientists and doctors had essentially no idea how lithium worked. A group of scientists mapped the response pathway of lithium using human induced pluripotent stem cells (hiPS), cells taken from bipolar patients and induced to behave like stem cells. A protein called CRMP2, involved in neuron signaling, was found to be inactive in bipolar patients. When lithium was added to a petri dish of hiPS cells, CRMP2 activity returned to normal. These results have been further verified by examining the brain tissue of deceased bipolar patients and finding a reduced amount of CRMP2 (MacDonald, 2017).

MacDonald, F. (2017, May 13). Finally, Scientists Think They Know How Lithium Treats Bipolar Disorder. Retrieved from https://www.sciencealert.com/finally-scientists-think-they-know-how-lithium-treats-bipolar-disorder

General Antipsychotics

Antipsychotics are used either on their own for mood stabilization or in conjunction with a mood stabilizer. They can serve as sedatives for anxiety, insomnia and agitation and irritability associated with both mania and depression. Olanzapine (Zyprexa), risperidone (Risperdol), quetiapine (Seroquel) and aripiprazole (Abilify) show more promise for treating mania. Only two antipsychotic treatments are approved for treating the depressive part of bipolar disorder: olanzapine in conjunction with fluoxetine (Zoloft) and quetiapine. The brain has a number of dopamine receptors, all labeled D1, D2, D3 and so on. Antipsychotics help relieve psychotic symptoms by reducing the signalling of D2 (Abi-Dargham et al., 2000) and by balancing D1 and D2 receptor pathways (Cazorla et al., 2014).

Abi-Dargham, A. et al. Increased baseline occupancy of D-2 receptors by dopamine in schizophrenia. Proc. Natl. Acad. Sci. USA 97, 8104–8109 (2000).

Cazorla, M. et al. Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry. Neuron 81, 153–164 (2014).

Vraylar

Vraylar is not necessarily a common medication for bipolar disorder, but it is worth mentioning because it is the least sedating out of all of the antipsychotics and is associated with the least weight gain. It is used to treat the mania associated with bipolar 1, but the FDA has not approved it yet for depression. It is a dopamine partial agonist and a dopamine regulator, so it can actually make people feel more awake, but Vraylar regulates dopamine at high levels that predispose a bipolar person to mania and keeps them from getting manic. Most antipsychotics work as dopamine antagonists, making the patient feel sleepy. It also acts as a serotonin agonist, helping to further balance mood and behavior (Kunzmann, 2019).

Kunzmann, K. (2019, January 15). Michael Thase, MD: Cariprazine and Current Bipolar Therapies. Retrieved from https://www.mdmag.com/medical-news/michael-thase-md-cariprazine-and-current-bipolar-therapies

Anti-Seizure Drugs

Some drugs originally used to treat epilepsy are now utilized to treat bipolar disorder. These drugs reduce electrical activity in the brain. These drugs include Depakote, Lamotrigine, Tegretol, Gabapentin and Topamax among others. Different anti-seizure medications are more inclined to treat different aspects of bipolar disorder. For example, Depakote and Tegretol are better at treating mania, while Lamotrigine is more effective at treating depression. Anti-seizure drugs, also known as anticonvulsants, work more rapidly than lithium (Purse, 2020).

Purse, M. (2020, February 7). How Can Anticonvulsants Help Treat Mania in Bipolar Disorder? Retrieved from https://www.verywellmind.com/anticonvulsants-for-treatment-of-mania-4006598