Creatine as a Novel Treatment for Depression in Females Using Methamphetamine: A Pilot Study.

OBJECTIVE: Depression among methamphetamine users is more prevalent in females than males, but gender-specific treatment options for this comorbidity have not been described. Reduced brain phosphocreatine levels have been shown to be lower in female methamphetamine users compared to males, and, of relevance, studies have demonstrated an association between treatment-resistant depression and reduced brain phosphocreatine concentrations. The nutritional supplement creatine monohydrate has been reported to reduce symptoms of depression in female adolescents and adults taking antidepressants, as well as to increase brain phosphocreatine in healthy volunteers. Therefore, the purpose of this pilot study was to investigate creatine monohydrate as a treatment for depression in female methamphetamine users. METHODS: Fourteen females with depression and comorbid methamphetamine dependence were enrolled in an 8-week open label trial of 5 g of daily creatine monohydrate and of these 14, 11 females completed the study. Depression was measured using the Hamilton Depression Rating Scale (HAMD) and brain phosphocreatine levels were measured using phosphorus magnetic resonance spectroscopy pre- and post-creatine treatment. Secondary outcome measures included anxiety symptoms, measured with the Beck Anxiety Inventory (BAI), as well as methamphetamine use, monitored by twice weekly urine drug screens and self-reported use. RESULTS: The results of a linear mixed effects repeated measures model showed significantly reduced HAMD and BAI scores as early as week 2 when compared to baseline scores. This improvement was maintained through study completion. Brain phosphocreatine concentrations were higher at the second phosphorus magnetic resonance spectroscopy scan compared to the baseline scan; Mbaseline = 0.223 (SD = 0.013) vs. Mpost-treatment = 0.233 (SD = 0.009), t (9) = 2.905, p <.01, suggesting that creatine increased phosphocreatine levels. Also, a reduction in methamphetamine positive urine drug screens of greater than 50% was observed by week 6. Finally, creatine was well tolerated and adverse events that were related to gastrointestinal symptoms and muscle cramping were determined as possibly related to creatine. CONCLUSIONS: The current study suggests that creatine treatment may be a promising therapeutic approach for females with depression and comorbid methamphetamine dependence. This study is registered on clinicaltrials.gov (NCT01514630).

Gender differences in the effect of tobacco use on brain phosphocreatine levels in methamphetamine-dependent subjects.

BACKGROUND: A high prevalence of tobacco smoking has been observed in methamphetamine users, but there have been no in vivo brain neurochemistry studies addressing gender effects of tobacco smoking in methamphetamine users. Methamphetamine addiction is associated with increased risk of depression and anxiety in females. There is increasing evidence that selective analogues of nicotine, a principal active component of tobacco smoking, may ease depression and improve cognitive performance in animals and humans. OBJECTIVES: To investigate the effects of tobacco smoking and gender on brain phosphocreatine (PCr) levels, a marker of brain energy metabolism reported to be reduced in methamphetamine-dependent subjects. METHODS: Thirty female and 27 male methamphetamine-dependent subjects were evaluated with phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) to measure PCr levels within the pregenual anterior cingulate, which has been implicated in methamphetamine neurotoxicity. RESULTS: Analysis of covariance revealed that there were statistically significant slope (PCr versus lifetime amount of tobacco smoking) differences between female and male methamphetamine-dependent subjects (p = 0.03). In females, there was also a statistically significant interaction between lifetime amounts of tobacco smoking and methamphetamine in regard to PCr levels (p = 0.01), which suggests that tobacco smoking may have a more significant positive impact on brain PCr levels in heavy, as opposed to light to moderate, methamphetamine-dependent females. CONCLUSION: These results indicate that tobacco smoking has gender-specific effects in terms of increased anterior cingulate high energy PCr levels in methamphetamine-dependent subjects. Cigarette smoking in methamphetamine-dependent women, particularly those with heavy methamphetamine use, may have a potentially protective effect upon neuronal metabolism.

A review of treatment options for co-occurring methamphetamine use disorders and depression.

Co-occurring methamphetamine use and depression interferes with treatment outcomes. Female methamphetamine users are known to have higher rates of depression than male methamphetamine users, although this is also true for the general population. There are limited treatment options for the management of depression among methamphetamine users. In this integrative review, we summarize data on treatment strategies for co-occurring depression and methamphetamine use disorders. English-language articles were identified from PsychINFO, CINAHL, PubMed, and Medline as well as from reference lists of key articles. Search terms included "methamphetamine," "depression," and "treatment." Research articles describing psychological (n = 3), pharmacological (n = 6), nutritional supplement (n = 1), and psychological combined with pharmacological (n = 3) approaches for the treatment of methamphetamine use or withdrawal and/or depression are included in this review. Psychological and combination of psychological with pharmacological approaches have not been shown to be effective in treating these co-occurring conditions. Antidepressants have been determined to be ineffective and/or to introduce side effects. Gender differences with response to treatment were examined in only one of the published studies. There is a large gap in knowledge regarding treatment of co-occurring methamphetamine use disorders and depression. Considering that female methamphetamine users experience higher rates of depression than men, a focus on gender-specific treatment approaches is warranted.

Decreased frontal lobe phosphocreatine levels in methamphetamine users.

BACKGROUND: Mitochondria-related mechanisms have been suggested to mediate methamphetamine (METH) toxicity. However, changes in brain energetics associated with high-energy phosphate metabolism have not been investigated in METH users. Phosphorus-31 ((31)P) magnetic resonance spectroscopy (MRS) was used to evaluate changes in mitochondrial high energy phosphates, including phosphocreatine (PCr) and ß-nucleoside triphosphate (ß-NTP, primarily ATP in brain) levels. We hypothesized that METH users would have decreased high-energy PCr levels in the frontal gray matter. METHODS: Study participants consisted of 51 METH (age=32.8±6.7) and 23 healthy comparison (age=31.1±7.5) subjects. High-energy phosphate metabolite levels were compared between the groups and potential gender differences were explored. RESULTS: METH users had lower ratios of PCr to total pool of exchangeable phosphate (PCr/TPP) in the frontal lobe as compared to the healthy subjects (p=.001). The lower PCr levels in METH subjects were significantly associated with lifetime amount of METH use (p=.003). A sub-analysis for gender differences revealed that female METH users, who had lower daily amounts (1.1±1.0g) of METH use than males (1.4±1.7g), had significantly lower PCr/TPP ratios than male METH users, controlling for the amount of METH use (p=.02). CONCLUSIONS: The present findings suggest that METH compromises frontal lobe high-energy phosphate metabolism in a dose-responsive manner. Our findings also suggest that the abnormality in frontal lobe high-energy phosphate metabolism might be more prominent in female than in male METH users. This is significant as decreased PCr levels have been associated with depressive symptoms, and poor responses to antidepressant treatment have been reported in those with decreased PCr levels.

Readiness to change in adults waiting for publicly funded substance abuse treatment.

The primary objective of this study was to evaluate the factor structure of a modified version of the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES) for a sample of indigent adults with alcohol and other drug problems. A community sample of 338 adults on waiting lists for entrance into publicly funded substance abuse treatment completed a 19-item modified version of the SOCRATES. Confirmatory factor analyses were conducted on two structural models of the SOCRATES based on prior literature. The results indicated that a two-factor model of the SOCRATES provided the best fit for the data in this study. Suggestions for future research using a modified version of this measure are discussed.