Other Antidepressant Medications


Category: Medical Options

What is it?

There are several types of drugs which fall under the broad banner of ‘antidepressants’ but are not part of the SSRIs, tricyclics, MAOIs or adrenergic groups. These other drugs are sometimes called ‘novel’ antidepressants. Some evidence is emerging for the use of these novel antidepressants in PTSD patients including:

  • Nefazodone (trade names include Avanza, Axit and Mirtazon)
  • Trazodone (trade names include Desyrel, Molipaxin, Trittico, Thombran, Trialodine and Trazorel)
  • Venlafaxine (trade names include Effexor, Efexor)
  • Mirtrazapine (trade names include Avanza, Axit and Mirtazon)
  • Bupropion (trade names include Wellbutrin, Zyban, Budeprion)

How does it work?

These antidepressants all have a different chemical make-up and thus have slightly different effects in the brain. The exact mechanism for their possible action on PTSD symptoms is not yet well understood. In the brain messages are passed between nerve cells via a synapse, a small gap between the cells. Naturally occurring chemicals known as neuro-transmitters allow the messages to pass across that gap. It is believed that incorrect levels of neuro-transmitters such as norepinephrine, dopamine and seratonin, lead to symptoms experienced by many PTSD patients. These antidepressant drugs may improve the balance of specific neuro-transmitters in the brain through various mechanisms and thus help to normalise brain function.

Is it effective?

The evidence for the effectiveness of novel antidepressant drugs for PTSD is variable and is discussed below.

  • Nefazodone - Some open-label trials of Nefazodone with PTSD patients have shown some reduction in symptom severity. However this research is of insufficient quality to establish the effectiveness or safety of this drug for PTSD.
  • Trazodone - Very little research has been done on the use of trazodone in PTSD and none have found it effective in treating the core symptoms of PTSD. Further research is required to establish the effectiveness and safety of trazodone in PTSD patients.
  • Venlafaxine - Very little research has been done on the use of venlafaxine in PTSD. One small trial found that venlafaxine significantly improved PTSD symptoms in some Bosnian refugees with PTSD, however much more research is required to establish the effectiveness and safety of this drug for PTSD patients.
  • Mirtrazapine - Very little research has been done on the use of mirtrazapine in PTSD. One small controlled trial found that patients using mirtrazapine had improved PTSD symptoms compared to those using placebos, but this did not reach statistical significance. Although this is promising, more research is required to establish the effectiveness and safety of mirtrazapine for PTSD patients.
  • Bupropoin - Very little research has been done on the use of bupropoin in PTSD. One small study found that veterans using bupropoin had modest improvement in combat-related PTSD symptoms but this did not reach statistical significance. Much more research is required to establish the effectiveness and safety of bupropoin for PTSD patients.

Are there any disadvantages?

Side effects are not uncommon and differ between the different medications and may include dry mouth, nausea, drowsiness, tremor, excessive sweating, increased appetite, vivid dreams, dizziness, and headache. Other side effects are possible and health practitioners should be made aware of any changes. Nefazodone has been linked to liver damage in some patients. Trazodone can be highly sedating in some people.

Where do you get it?

These antidepressant drugs can only be prescribed by registered health practitioners.

What are the evidence limitations?

The evidence base for ‘novel’ antidepressant medication use in PTSD is limited. Studies to date have been on small numbers of patient or of low quality. The methods of diagnosing PTSD were not reported in the review literature. Therefore interpreting this evidence should be undertaken with caution.


Based on the current limited evidence nefazodone, trazodone, venlafaxine, mirtrazapine and bupropion cannot be recommended for PTSD. More research is required to establish the effectiveness and safety of these drugs for PTSD patients. It is important that any drug treatment is provided by a registered health professional, with appropriate assessment carried out prior to treatment as well as ongoing monitoring during the course of treatment.

Key References

Canive, JM, Clark, RD, Calais, LA, et al. 1998, ‘Bupropion treatment in veterans with posttraumatic stress disorder: an open study’, Journal of Clinical Psychopharmacology, vol. 18, pp. 379-383.

Cooper, J, Carty, J, Creamer, M 2005, ‘Pharmacotherapy for posttraumatic stress disorder: empirical review and clinical recommendations’, Australian and New Zealand Journal of Psychiatry, vol. 39, pp.674-682.

Davidson, JR, Weisler, RH, Butterfield, MI et al. 2003, ‘Mirtazapine vs placebo in posttraumatic stress disorder: a pilot trial’, Biological Psychiatry, vol. 53, pp. 188-191.

Hertzberg, MA, Feldman, ME, Beckham, JC, et al. 1996, ‘Trial of trazodone for posttraumatic stress disorder using a multiple baseline group design’, Journal of Clinical Psychopharmacology, vol. 16, pp. 294-298.

Hidalgo, R, Hertzberg, MA, Mellman, T et al. 1999, ‘Nefazodone in post-traumatic stress disorder: results from six open-label trials’, International Clinical Psychopharmacology, vol. 14, pp. 61-68.

Mellman, TA, David, D & Barza, L 1999, ‘Nefazodone treatment and dream reports in chronic PTSD’, Depression and Anxiety, vol. 9, pp. 146-148.

Schoenfeld, F, Marmar, C & Neylan, T 2004, ‘Current concepts in pharmacotherapy for posttraumatic stress disorder’, Psychiatric Services, vol. 55, pp. 519-531.

Smajkic, A, Weine, S, Duric-Bijedic, Z, Boskailo, E, Lewis, J & Pavkovic, I et al. 2001, ‘Sertraline, paroxetine, and venlafaxine in refugee posttraumatic stress disorder with depression symptoms’, Journal of Traumatic Stress, vol. 14, pp. 445-452

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