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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), 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Another notable agent is rimonabant, a cannabinoid receptor antagonist marketed as an anti-obesity agent which was withdrawn shortly after its introduction due to the incidence of severe psychiatric side effects associated with its use including depression, anxiety, and suicidal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),[8][7] and dynorphin.[10]

See alsoEdit


  1. 1.0 1.1 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.
  2. Belmaker RH (August 2008). The future of depression psychopharmacology. CNS Spectrums 13 (8): 682–7.
  3. Beers MH, Passman LJ (December 1990). Antihypertensive medications and depression. Drugs 40 (6): 792–9.
  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.
  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.
  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.
  7. 7.0 7.1 7.2 Norman TR, Burrows GD (February 2007). Emerging treatments for major depression. Expert Review of Neurotherapeutics 7 (2): 203–13.
  8. 8.0 8.1 Stokes PE, Sikes CR (February 1988). The hypothalamic-pituitary-adrenocortical axis in major depression. Neurologic Clinics 6 (1): 1–19.
  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.
  10. Knoll AT, Carlezon WA (February 2010). Dynorphin, stress, and depression. Brain Research 1314: 56–73.

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