Rasagiline (Azilect)

Primer

Rasagiline is a monoamine oxidase inhibitor (MAOI). It is used in the treatment of Parkinson's disease.

Indications

Non-Motor Symptoms

  • Several randomized control trials and observational studies have shown improved depression symptoms, improved cognition, reduced fatigue, improved total sleep time, reduced sleep latency, and reduced daytime sleepiness.[1][2]
  • Another randomized control trial showed that rasagiline did not have any significant effects versus placebo on depressive symptoms or cognition in Parkinson's patients with moderate depressive symptoms.[3]

Dosing

Contraindications

Interaction with Antidepressants

  • Since rasagiline is a monoamine oxidase B (MAO-B) inhibitor, concerns have been raised about the risk for serotonin syndrome if rasagiline is taken concurrently with serotonergic antidepressants.
    • There are multiple case reports and post-marketing reports of serotonin syndrome in patients taking a combination of rasagiline and an antidepressant.[4][5][6]
    • However, there are also multiple case reports and randomized control trials (ADAGIO, LARGO, TEMPO[7]) of participants taking taking both rasagiline and an antidepressant (serotonin reuptake inhibitors, tricyclic antidepressants, or serotonin-norepinephrine reuptake inhibitors) and did not have any cases of serotonin syndrome during the study period.[8][9]
    • If combining rasagiline with an antidepressant, careful monitoring for any signs of serotonin syndrome needs to be carried out.

Mechanism of Action

  • Rasagiline is a centrally acting monoamine oxidase type B (MAO-B) inhibitor.
    • It increases dopamine levels by these drugs reducing the breakdown of dopamine generated from levodopa in the central nervous system.

References

1) Smith, K. M., Eyal, E., Weintraub, D., & Adagio Investigators. (2015). Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA neurology, 72(1), 88-95.
2) Schettino, C., Dato, C., Capaldo, G., Sampaolo, S., Di Iorio, G., & Melone, M. A. (2016). Rasagiline for sleep disorders in patients with Parkinson’s disease: a prospective observational study. Neuropsychiatric Disease and Treatment, 2497-2502.
3) Barone, P., Santangelo, G., Morgante, L., Onofrj, M., Meco, G., Abbruzzese, G., ... & Tinazzi, M. (2015). A randomized clinical trial to evaluate the effects of rasagiline on depressive symptoms in non‐demented Parkinson's disease patients. European journal of neurology, 22(8), 1184-1191.
4) Hébant, B., Guillaume, M., Desbordes, M., Gaillon, G., Maltête, D., & Lefaucheur, R. (2016). Combination of paroxetine and rasagiline induces serotonin syndrome in a parkinsonian patient. Revue Neurologique, 172(12), 788-789.
5) Supasyndh, O. (2015). Combination of escitalopram and rasagiline induced serotonin syndrome: a case report and review literature. J Med Assoc Thai, 98(12), 1254-7.
6) Duval, F., Flabeau, O., Razafimahefa, J., Spampinato, U., & Tison, F. (2013). Encephalophaty associated with rasagiline and sertraline in Parkinson's disease: possible serotonin syndrome. Movement Disorders, 28(10), 1464-1464.
7) Nayak, L., & Henchcliffe, C. (2008). Rasagiline in treatment of Parkinson’s disease. Neuropsychiatric Disease and Treatment, 4(1), 23-32.
8) Smith, K. M., Eyal, E., Weintraub, D., & Adagio Investigators. (2015). Combined rasagiline and antidepressant use in Parkinson disease in the ADAGIO study: effects on nonmotor symptoms and tolerability. JAMA neurology, 72(1), 88-95.
9) Kaur, N., Madan, R., & Sharma, A. (2012). Successful use of rasagiline in combination with two antidepressants: a case report. Innovations in clinical neuroscience, 9(11-12), 39.