Overall, self-reported measures of depression, anxiety and methamphetamine withdrawal symptoms decreased significantly during the first two weeks of the residential stay with the most dramatic reduction occurring during the first week. These results differ somewhat from those of a previous study by McGregor and colleagues11
, which demonstrated a decline in methamphetamine withdrawal severity approaching control levels within one week. The reason for this is unclear, but may be due to the fact that several patients in the McGregor study received low dose benzodiazepines, which may have affected measures of methamphetamine withdrawal. Additionally, participants in the current study were older and had used methamphetamine longer. These differences may have contributed to the longer duration of withdrawal symptoms in the current study, suggesting that the duration of methamphetamine withdrawal-related symptoms may be longer than previously reported.
Although sitting diastolic blood pressure did increase significantly between weeks 3 and 4, values were never outside of clinically acceptable normal ranges. These findings are consistent with results from those of McGregor, et. al.11
, in that radial pulse and blood pressure did not change significantly and stayed within normal limits for the duration of the 3 week study. Be that as it may, the clinical utility of these measures are unclear in monitoring methamphetamine withdrawal during early treatment.
Self-report measures of refreshed sleep improved significantly during the first week in treatment; however, although this improvement persisted for refreshed sleep, quality of sleep significantly worsened during the second week of the residential stay. This would seem to indicate that, although the amount of sleep in abstinent methamphetamine users may stabilize fairly quickly as demonstrated in the previous study by McGregor et. al.11
, sleep quality may be a complex phenomenon that does not stabilize as rapidly. It is also somewhat unclear why seemingly related measures of refreshed sleep and quality of sleep don't follow a similar pattern. These somewhat inconsistent findings suggest that a closer examination of sleep to include more objective measures of sleep, such as actigraphic monitoring, is warranted.
Cognitive testing did not reveal significant changes during the course of the study, although performance did appear to decline during the second week of treatment. This is in contrast to previous studies that have demonstrated significant problems in cognitive function in non-treatment seeking, recently abstinent methamphetamine dependent individuals25, 26
. The previous studies are difficult to compare to the current study as these previous studies were in non-treatment seeking methamphetamine dependent individuals and all results were based on comparisons to controls. It should be noted, however, that the negative results of the present study may be due to the small sample size, which is less than 33% of that for previous studies25, 26
. Thus, these negative results may be due to a lack of power as well as differences in sample populations. These findings also suggest that subjective ratings are much more robust than cognitive measures in detecting changes following abrupt termination of amphetamine administration.
The small sample size (N=6) is a significant limitation of the current study and does limit generalizability for the overall population of methamphetamine dependent patients entering inpatient treatment. The lower than expected recruitment of eligible methamphetamine users over an 18-month time frame occurred due to several factors: staff did not always remember to refer potential participants, RCA contacts were recommending potential patients to be abstinent prior to their admission to the facility, which was an exclusion criterion, and comorbidity and/or use of psychoactive medications was prevalent in these patients. These factors highlight the difficulties with conducting studies like this in real world situations. Although interpretation of findings was sometimes difficult because the power to detect significant differences may have been too low, that significant changes in some sleep, withdrawal and anxiety/mood measures occurred indicate that these symptoms may be the result of a pharmacological effect associated with cessation of methamphetamine use. . An alternate explanation is that the declines in these measures are not due to resolving drug withdrawal per se, but rather reflect an improvement in anxiety and mood symptoms as patients settle into the supportive treatment milieu, engage in therapy, and consequently report fewer subjective symptoms of withdrawal. A placebo controlled, double-blind study is necessary to more closely examine the potential contribution of treatment milieu effects relative to the pharmacological effects associated with methamphetamine cessation as well as the effects of methamphetamine withdrawal on relapse and treatment retention. Although medications that reduce symptoms associated with withdrawal may be extremely valuable in promoting engagement and retention in behavioral and psychosocial treatment27, 28
, future studies need to more closely examine the impact of these withdrawal symptoms on treatment outcome. The small number of study participants also likely limited our ability to find significant changes in cognitive functioning that have previously been demonstrated25, 26
Another major limitation of the study is that it was uncontrolled; that is, there was no control for the abstinent condition. However, these findings will aid the development of a double-blind, placebo-controlled withdrawal paradigm to control for expectancy and define more precisely the severity and time-course of methamphetamine withdrawal as well as examine the efficacy of potential pharmacotherapies for alleviating these symptoms.