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Chan B, Kondo K, Ayers C, et al. Pharmacotherapy for Stimulant Use Disorders: A Systematic Review [Internet]. Washington (DC): Department of Veterans Affairs (US); 2018 Aug.
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| Reviewer Number | Comment | Author response |
|---|---|---|
| Are the objectives, scope, and methods for this review clearly described? | ||
| 1 | Yes | Noted. |
| 3 | Yes | Noted. |
| 5 | Yes | Noted. |
| 6 | Yes | Noted. |
| 7 | Yes | Noted. |
| Is there any indication of bias in our synthesis of the evidence? | ||
| 1 | No | Noted. |
| 3 | Yes - I am concerned that relying on review papers may have biased the results slightly see below | By necessity this review was broadly scoped. There is good precedent for using systematic reviews for this process. |
| 5 | No | Noted. |
| 6 | No | Noted. |
| 7 | No | Noted. |
| Are there any published or unpublished studies that we may have overlooked? | ||
| 1 | Yes - 3 papers: Kampman paper on propranolol; Carroll paper on psychotherapy and disulfiram; Kosten paper on disulfiram and genetics. The latter 2 are provided in the attachment. | We had identified and included the Kampman 2001 study of propranolol, but inadvertently omitted it from the draft report; we have made this correction and added it to the section on Other Pharmacotherapies. We examined the Carroll 2004 study, which was identified in an included systematic review (Pani 2010), but we were not able to combine the outcomes with other studies in meta-analysis. The Kosten paper on disulfiram and genetics has been incorporated in KQ2. |
| 3 | Yes - The use of reviews may have led to insufficient weight being given to the evidence supporting some medications, for instance topiramate | As mentioned above there is good precedent for the use of reviews. However, one of the SRs (Minozzi 2015) did not examine continuous abstinence as an outcome. Subsequently, we abstracted data on continuous abstinence from the included RCTs and this did reveal positive findings on topiramate which are now included in this report. |
| 5 | Yes - See Comments from Reviewer 5 below | Noted. |
| 6 | No | Noted. |
| 7 | No | Noted. |
| Additional suggestions or comments can be provided below. | ||
| 1 | There are multiple wording issues. The provision of data from the ASI makes no sense throughout the synthesis and needs to be corrected. Many other specific suggestions are included below. | Wording issues have been addressed. We agree that the ASI drug composite metric may not be meaningful since the ASI score is not specific to stimulant use. While our initial aim was to abstract addiction severity as a population characteristic, we agree that there is no clear way to present severity for comparison across studies due to variability in reporting and metrics used. We have therefore removed addiction severity from the tables altogether. |
| 3 | The use of red and green as highlighting color for the tables is difficult for those who are red green colorblind. | We considered this limitation of the color choices, and selected hues with varying levels of saturation that were distinguishable on hardcopy when printed in greyscale. |
| 3 | There are now two positive trials of the combination of Adderall and topiramate for the treatment of cocaine use disorder. One is referenced, the second is being presented at CPDD 13 June. | We included a study published in 2012 among the section of “Other Pharmacotherapies” in KQ1, and noted a positive effect of topiramate combined with mixed amphetamine salts. We looked into the recently completed trial of Adderall-ER combined with topiramate for cocaine dependence (NCT01811940) as suggested, but the findings of this study were not yet available at the time of this writing. |
| 6 | Nice job! No further comments. | Noted, thank you. |
| 1 | Page 2; line 12: Not clear if “withdrawals” here means a physiologic withdrawal syndrome or dropout from treatment. | We have clarified the wording to mean dropout from treatment. |
| 1 | Page 2; line 45: We may have missed propranolol and doxazosin. | The Shorter, 2013 study in the “Other Pharmacotherapies” section examined the effects of doxazosin. We had included a study on propranolol (Kampman 2001) but had mistakenly omitted it from the narrative; we have corrected this error. |
| 1 | Page 6; line 20: These medications all work in the brain, so why would they not be considered psychopharmacotherapies. The distinction is unclear. | We agree, and have changed the category of “psychopharmacotherapies” to “mental health pharmacotherapies”. |
| 1 | Page 11; line 9: Change to “stimulant use disorder.” | Done. |
| 1 | Page 11; line 44: It is not alternative or concurrent, it is offered as the primary treatment modality. | We have revised the sentence accordingly. |
| 1 | Page 11; line 46: Add “treatment” before “retention.” | Done. |
| 1 | Page 13; line 43: Treatment retention and dropout are really the same outcome, and both probably do not need to be mentioned. | We have made the suggested change. |
| 1 | Page 20; line 15: Do not capitalize acamprosate | Done. |
| 1 | Page 22; line 28: specify treatment dropout or study withdrawal here so as not to confuse with physiologic cocaine withdrawal. | Done. |
| 1 | Page 24; line 49: Hard to grasp this row when it breaks across pages. | We have adjusted the rows as suggested. |
| 1 | Page 28; line 52: Resperpine is not really an antipsychotic. | We understand that this isn’t a perfect characterization, however we are using the classification that Cochrane used. Additionally, changing the class would not change the conclusions. |
| 1 | Page 30; line 20: selegeline in an MAO inhibitor, not a stimulant, although l-amphetamine is a metabolite. | We understand that this isn’t a perfect characterization, however we are using the classification that Cochrane used. Additionally, changing the class would not change the conclusions. |
| 1 | Page 37; line 8: Not sure why Carroll, K. M., L. R. Fenton, S. A. Ball, C. Nich, T. L. Frankforter, J. Shi and B. J. Rounsaville (2004). “Efficacy of disulfiram and cognitive behavior therapy in cocainedependent outpatients: a randomized placebocontrolled trial.” Archives of General Psychiatry 61(3): 264–272. is not included. | The Carroll 2004 paper was identified in an included systematic review (Pani, 2010). We examined the Carroll 2004 study for inclusion in our metaanalyses, but the reported outcomes were not combinable with other studies. |
| 1 | Page 39; line 39: Injectable should be sublingual. | We have made the correction as suggested. |
| 1 | Page 45; line 42: change 280 to 380 | We corrected this error. |
| 1 | Page 60; line 22: What about, Kosten et al., Pharmacogenetic randomized trial for cocaine abuse: disulfiram and dopamine β-hydroxylase. Biol Psychiatry. 2013 Feb 1;73(3):219–24. doi: 10.1016/j.biopsych.2012.07.011. | We have added this study as suggested. |
| 1 | Page 68; line 43: Don’t understand “study duration use.” | We have clarified the wording to convey use during the study period. |
| 1 | Page 69; line 5: treatment withdrawals | Noted. |
| 1 | Page 76; line 22: This sentence is in contradiction to one two paragraphs below (Line 41) | We have corrected the inconsistency. |
| 1 | Page 92; line 6: You may be lumping cocaine studies and methamphetamine studies together here. If so, you need to explain that point. | We have separated the cocaine and methamphetamine studies in the analysis of contingency management, and included them with the respective sections on subgroup analyses (KQ2 and KQ4). |
| 1 | Page 93; line 23: treatment withdrawal or dropout. | We have made this change throughout the review. |
| 5 | Page 92: The Contingency Management (CM) section of the review reports “there was no significant difference between studies that did vs. did not use contingency management in proportion of subjects who completed treatment.” This can easily be misinterpreted to mean that CM has no effect on treatment retention in general, not just in pharmacotherapy trials. In fact, several studies have demonstrated a treatment retention benefit associated with CM. The attendance rates for prize CM in the published literature range from as high as 70.5% (Petry, Alessi, Carroll, et al., 2006) to as low as 45% (Petry, Weinstock, Alessi, et al., 2010). In the VA’s national implementation of CM, patients attended 55.9% of sessions delivered twice-weekly over 12 weeks (DePhilippis et al., 2018). Because patients in the VA initiative included those who were initially-abstinent and those who were not, the study by Petry and colleagues (2012) that examined differential outcomes by initial abstinence status provides the most appropriate comparison. That study found an attendance rate of 67.1% for patients initially abstinent and 46.7% for patients who began treatment with a positive sample (Petry, Barry, Alessi, et al., 2012). The attendance rate (55.9%) observed among VA’s CM patients is about the average of these two rates. Furthermore, in the VA’s CM implementation, fifty percent of CM patients completed 14 or more CM sessions within the designated treatment period (typically 12 weeks) (DePhilippis et al., 2018). In comparison, Oliva et al. (2013) found that only 42% of VA patients with an outpatient SUD treatment episode completed more than two sessions of care in a one year period. Petry, N.M., Alessi, S.M., Carroll, K.M., Hanson, T., MacKinnon, S., Rounsaville, B., Sierra, S., 2006. Contingency management treatments: Reinforcing abstinence versus adherence with goal-related activities. J. Consult. Clin. Psychol., 74(3), 592–601. doi:10.1037/0022–006X.74.3.592 Petry, N.M., Weinstock, J., Alessi, S.M., Lewis, M.W., Dieckhaus, K., 2010b. Group-based randomized trial of contingencies for health and abstinence in HIV patients. J. Consult. Clin. Psychol., 78(1), 89–97. doi:10.1037/a0016778. Oliva, E.M., Bowe, T., Sox-Harris, A.H., Trafton, J.A., 2013. False Starts in Psychotherapy for Substance Use Disorders and PTSD in the VHA. Psychiatric Services, 64(8), 722. doi:10.1176/appi.ps.201300145. DePhilippis, D., Petry, N.M., Bonn-Miller, M.O., Rosenbach, S.B., McKay, J.R. (2018). The national implementation of Contingency Management (CM) in the Department of Veterans Affairs: Attendance at CM sessions and substance use outcomes. Drug and Alcohol Dependence, 185, 367–373. doi: 10.1016/j.drugalcdep.2017.12.020 | Noted. We have added clarification on the efficacy of CM, specifically that the efficacy of the pharmacotherapy didn’t change based on CM, but that this observation is limited by very few studies that directly compared the use of CM. |
| 5 | Page 1, Line 8: change ‘Stimulant abuse and dependence’ to the new, DSM-V nomenclature of ‘Stimulant use disorder.’ | We have made the suggested change. |
| 5 | Page 11, Line 16: change ‘dependence or abuse’ to ‘substance use disorder.’ | We have made the suggested change. |
| 5 | Page 11, Lines 39–48: The review should note that contingency management among the treatments available for ‘stimulant addiction.’ | We have made this change. |
| 5 | Page 48, Section on Anticonvulsants: The review appears to have excluded a RCT by Kampman and colleagues (2004) that found “topiramate-treated subjects were more likely to be abstinent from cocaine compared to placebo-treated subjects (Z=2.67, P=0.01). Topiramate-treated subjects were also more likely to attain 3 weeks of continuous abstinence from cocaine (χ2=3.9, d.f.=1, P=0.05).” Kampman, K.M., Pettinati, H., Lynch, K.G., Dackis, C., Sparkman, T., Weigley, C., O’Brien, C.P., Kampman, K.M., Pettinati, H., Lynch, K.G., Dackis, C., Sparkman, T., Weigley, C., O’Brien, C.P., 2004. A pilot trial of topiramate for the treatment of cocaine dependence. Drug Alcohol Depend. 75, 233–240. | This RCT was included in the Minozzi 2015 systematic review. Per our protocol, we did not write up the results of the individual trials in the SR, and relied on the conclusions of the SR authors. Upon review, it seems that because continuous abstinence was not an outcome of interest in the Minozzi 2015 review, we did not abstract that information, and hence the findings of that study were overlooked. We have now analyzed the RCTs from the review that reported continuous abstinence, including the 2004 Kampman study and incorporated these findings in the report. |
| 5 | Page 59, Section entitled “Comorbid or Lifetime Alcohol Use Disorder”: The review neglected to include the Kampman et al. 2013 RCT examining topiramate among patients with co-morbid cocaine and alcohol dependence. The study is cited elsewhere in the review and is reference 42 in the Reference section of the review. | This study was not included in this section because we were only looking at studies that had a comparison group. All patients in this trial had comorbid cocaine and alcohol dependence. |
| 5 | Page 80, Section on ‘Pharmacotherapies for other SUDs’: In subsection including naltrexone is mistakenly named ‘Opioid Agonists.’ Naltrexone is a full opioid antagonist. | We have made this correction. |
- Peer Reviewer Comments and Author Responses - Pharmacotherapy for Stimulant Use ...Peer Reviewer Comments and Author Responses - Pharmacotherapy for Stimulant Use Disorders: A Systematic Review
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