Table 3.
Open trials evaluating the effects of investigational drugs on the treatment of PTSD: Monoamine mechanisms.
| Drug | Primary Mechanism | Pavlovian FC Process* | Population/Primary Outcome | Trial Type/# Enroll | Start Date/Estimated Completion | Comment |
|---|---|---|---|---|---|---|
| Propanolol | NE: b receptor antagonist | # Acquisition | Chronic PTSD | DBPC/50 | Feb 2010 | Single dose with memory reactivation each week for six weeks. Evaluation at baseline and after 8 weeks |
| $ Consolidation | CAPS | Jun 2012 | ||||
| # Retrieval | ||||||
| # Incubation | ||||||
| # Reconsolidation | ||||||
| $ Extinction | ||||||
| PTSD and non-PTSD with distress | DBPC/66 | Feb 2010 | Single treatment with memory reactivation. Assessments at baseline and after 4 weeks | |||
| CAPS, IES, TMDM | Sep 2011 | |||||
| Chronic PTSD, military-related | DBPC/60 | Sep 2007 | Single treatment with memory reactivation. Measurements pre and post-treatment | |||
| Psychophysiologic Responses | Oct 2012 | |||||
| Chronic PTSD with Alcohol Depend. | DBPC/50 | Jan 2010 | Propranolol coupled with the elicitation/retrieval of trauma-related memories. Single treatment with 2 week follow-up | |||
| Subjective Distress | Aug 2012 | |||||
| Prazosin | NE: a1 receptor antagonist | ” Acquisition | Chronic PTSD, military-related | DBPC/326 | Jan 2010 | Titrated to stable daily dose to be maintained throughout study. Evaluate changes versus baseline at 6, 10, 14, 18, 22 and 26 weeks |
| $ Consolidation | Nightmares, sleep quality and quantity, and global clinical status | Mar 2013 | ||||
| # Extinction | ||||||
| Chronic PTSD, military-related | DBPC/300 | Sep 2009 | Treatment for 15 weeks to test augmentation of previous psychotropic medications and/or psychotherapy | |||
| CAPS, PSQI, CGIC | Jun 2014 | |||||
| Yohimbine | NE: a2 receptor antagonist | ” Acquisition | Chronic PTSD, military-related | DBPC/60 | Dec 2010 | Yohimbine given one hour before first imaginal exposure in PE. Evaluation at baseline, 15 weeks and 27 weeks |
| $ Retrieval | CAPS | May 2015 | ||||
| ” Extinction | ||||||
| Sertraline | 5-HT: SSRI | # Retrieval | Chronic PTSD, military-related | DBPC/441 | Nov 2011 | Treatment with up to 13 sessions of PE therapy +24 weeks of daily sertraline compared to placebo +PE |
| CAPS | Dec 2015 | |||||
| Venlafaxine | 5-HT, NE: SNRI | ” Extinction | PTSD | OL/150 | Apr 2012 | Six months of daily treatment with venlafaxine combined with CBT compared to sertraline + CBT |
| HTQ | Apr 2014 | |||||
| Mirtazapine | TCA, SSRI | # Retrieval | Chronic PTSD | DBAC | Jun 2010 | Daily doses for 12 weeks. Patients that respond will continue treatment another 12 weeks |
| Sertraline | CAPS and time to discont | 60 | Jun 2013 | |||
| MDMA | 5HT: releaser, reuptake inhibitor (DA, NE) | untested | Chronic PTSD, military-related | DBPC | Sep 2010 | Introductory 90 min psychotherapy followed by two 8 h sessions 3 – 5 weeks apart and combined with MDMA. |
| CAPS | 24 | Dec 2013 | ||||
| Evaluations at baseline; at 1 month following session 2; at 2 months following session 3 and at 12 months | ||||||
| Methylene Blue | MAO: Inhibitor | ” Extinction | Chronic PTSD | DBPC | Sep 2009 | Daily psychotherapy followed by a dose of methylene blue. |
| PTSD symptom severity | 42 | Apr 2013 | Assessment at pre- and post-treatment, 1 and 3 months | |||
| PRX-03140 | 5HT: 5HT4 partial agonist | untested | Chronic PTSD | OL/12 | Apr 2012 | PRX-03140 given daily for 10 weeks with dose escalation |
| Change in adverse events | Dec 2012 |
Source: ClinicalTrials.gov.
Effects of drugs on Pavlovian FC processes: ” = enhanced, # = impaired, $mixed results. No entry means either the drug has not been tested for that process or available tests show null effects. Both preclinical and clinical studies were considered, but only if drugs were evaluated on explicit FC paradigms. Acquisition: refers to a clear learning effect (either within-session or STM effect, or effect with pre-training but not post-training administration); Consolidation: refers to a clear consolidation effect (drug given post-training but washed out before fear retrieval test). FC is used when data aren't available to distinguish between acquisition and consolidation effects (Note: Pavlovian FC Processes column excludes findings from instrumental avoidance studies).
CAPS: Clinician-Administered PTSD Scale; CGIC: Clinical Global Impression of Change Scale; DBAC: Double Blind Active Control; FC: Fear Conditioning; HTQ: Harvard Trauma Questionnaire; IES: Impact of Event; POMS: Profile of Mood States; PSQI: Pittsburgh Sleep Quality Index; TMDM: Traumatic Memory Description Measure.