A depressogen is a substance 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 ethanol, 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., leuprorelin, 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Another notable agent is rimonabant, a cannabinoid receptor antagonist marketed as an anti-obesity agent which was withdrawn shortly after its introduction due to the incidence of severe psychiatric side effects associated with its use including depression, anxiety, and suicidal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), tachykinins (e.g., substance P),[7] glucocorticoids (e.g., cortisol, cortisone),[7][8] and dynorphin.[9]

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  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. doi:10.31887/DCNS.2011.13.1/ccelano. PMC 3181967. PMID 21485751.
  2. ^ Belmaker RH (August 2008). "The future of depression psychopharmacology". CNS Spectrums. 13 (8): 682–7. doi:10.1017/S1092852900013766. PMID 18704023. S2CID 33347610.
  3. ^ Beers MH, Passman LJ (December 1990). "Antihypertensive medications and depression". Drugs. 40 (6): 792–9. doi:10.2165/00003495-199040060-00003. PMID 2078996. S2CID 2052978.
  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. doi:10.1097/01.WNF.0000228369.25593.35. PMID 16960470. S2CID 248730.
  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. doi:10.1111/j.1527-3458.2006.00053.x. PMC 6741762. PMID 16834758.
  6. ^ Moreira FA, Crippa JA (June 2009). "The psychiatric side-effects of rimonabant". Revista Brasileira de Psiquiatria. 31 (2): 145–53. doi:10.1590/s1516-44462009000200012. PMID 19578688.
  7. ^ a b c Norman TR, Burrows GD (February 2007). "Emerging treatments for major depression". Expert Review of Neurotherapeutics. 7 (2): 203–13. doi:10.1586/14737175.7.2.203. PMID 17286553. S2CID 28998898.
  8. ^ a b Stokes PE, Sikes CR (February 1988). "The hypothalamic-pituitary-adrenocortical axis in major depression". Neurologic Clinics. 6 (1): 1–19. doi:10.1016/S0733-8619(18)30881-8. PMID 2837631.
  9. ^ Knoll AT, Carlezon WA (February 2010). "Dynorphin, stress, and depression". Brain Research. 1314: 56–73. doi:10.1016/j.brainres.2009.09.074. PMC 2819644. PMID 19782055.