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A depressogenic substance (or depressogen) is one that causes or can cause depression, usually as a side effect.[1] They are the functional opposites of antidepressants.[2]

Examples of drugs commonly associated with depressogenic effects include some anticonvulsants such as the barbiturates (e.g. phenobarbital), benzodiazepines (e.g. diazepam), vigabatrin, and topiramate, corticosteroids like dexamethasone and prednisone, cytokines like interferon-α and interleukin-2, certain antihypertensives such as amiodarone, clonidine, methyldopa, reserpine, and tetrabenazine (used as an antipsychotic/antihyperkinetic),[3][4] and agents with antiandrogen, antiestrogen, and/or anti-neurosteroid activities such as GnRH agonists (e.g., leuprolide, goserelin), anastrozole (an aromatase inhibitor), finasteride (a 5α-reductase inhibitor),[5] and clomiphene (a SERM), as well as others including flunarizine, mefloquine, and efavirenz.[1] Another notable agent is rimonabant, a cannabinoid receptor antagonist marketed as an anti-obesity agent which was withdrawn shortly after its introduction due to the incidence of severe psychiatric side effects associated with its use including depression, anxiety, and suicidal ideation.[6]

Examples of endogenous compounds that have been implicated in stress and depression include corticotropin-releasing hormone (CRH),[7][8] cytokines (e.g., interferon-α, interleukin-2),[9] tachykinins (e.g., substance P),[7] glucocorticoids (e.g., cortisol, cortisone),[7][8] and dynorphin.[10]

See also[edit]


  1. ^ a b Celano CM, Freudenreich O, Fernandez-Robles C, Stern TA, Caro MA, Huffman JC (2011). "Depressogenic effects of medications: a review". Dialogues in Clinical Neuroscience. 13 (1): 109–25. PMC 3181967Freely accessible. PMID 21485751. 
  2. ^ Belmaker RH (August 2008). "The future of depression psychopharmacology". CNS Spectrums. 13 (8): 682–7. PMID 18704023. 
  3. ^ Beers MH, Passman LJ (December 1990). "Antihypertensive medications and depression". Drugs. 40 (6): 792–9. PMID 2078996. doi:10.2165/00003495-199040060-00003. 
  4. ^ Kenney C, Hunter C, Mejia N, Jankovic J (2006). "Is history of depression a contraindication to treatment with tetrabenazine?". Clinical Neuropharmacology. 29 (5): 259–64. PMID 16960470. doi:10.1097/01.WNF.0000228369.25593.35. 
  5. ^ Finn DA, Beadles-Bohling AS, Beckley EH, et al. (2006). "A new look at the 5alpha-reductase inhibitor finasteride". CNS Drug Reviews. 12 (1): 53–76. PMID 16834758. doi:10.1111/j.1527-3458.2006.00053.x. 
  6. ^ Moreira FA, Crippa JA (June 2009). "The psychiatric side-effects of rimonabant". Revista Brasileira De Psiquiatria (São Paulo, Brazil : 1999). 31 (2): 145–53. PMID 19578688. doi:10.1590/s1516-44462009000200012. 
  7. ^ a b c Norman TR, Burrows GD (February 2007). "Emerging treatments for major depression". Expert Review of Neurotherapeutics. 7 (2): 203–13. PMID 17286553. doi:10.1586/14737175.7.2.203. 
  8. ^ a b Stokes PE, Sikes CR (February 1988). "The hypothalamic-pituitary-adrenocortical axis in major depression". Neurologic Clinics. 6 (1): 1–19. PMID 2837631. 
  9. ^ Gibb J, Audet MC, Hayley S, Anisman H (2009). "Neurochemical and behavioral responses to inflammatory immune stressors". Frontiers in Bioscience (Scholar Edition). 1: 275–95. PMID 19482702. doi:10.2741/e26. 
  10. ^ Knoll AT, Carlezon WA (February 2010). "Dynorphin, stress, and depression". Brain Research. 1314: 56–73. PMC 2819644Freely accessible. PMID 19782055. doi:10.1016/j.brainres.2009.09.074.