Creatine as a Treatment Option for Depression in Methamphetamine Using Females
Condition: Depression; Substance Abuse; Substance Use; Neuroimaging; Dual Diagnosis
MeSH terms: Substance-Related Disorders; Depression; Depressive Disorder
Intervention: Creatine monohydrate
Intervention description: Five grams of creatine monohydrate will be administered for eight weeks.
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 14.0
Sex: Female
Minimum age: 13 Years
Maximum age: 64 Years
Healthy volunteers: No

Summary:

      Methamphetamine (MA) is a psychostimulant drug with high abuse potential. MA can be smoked,
      snorted, injected or ingested orally to produce a release of high levels of dopamine into the
      brain and reduction of dopamine uptake. Its use results in feelings of pleasure, increased
      energy, and greater alertness lasting up to 12 hours. In 2010, the National Survey on Drug
      Use and Health reported that 353,000 Americans aged 12 or older reported being current MA
      users. Over the past decade MA use rates have fluctuated with current use rates on the
      decline; however, importantly, even though overall use rates are declining, use rates among
      males and females are approaching equal proportions. This use rate pattern is unlike other
      drugs of abuse, which typically demonstrate males using more than females. In some states,
      more females than males consider MA as their drug of choice. Namely, in a 2010 report in the
      state of Utah, more females were diagnosed with MA as a primary substance of abuse than males
      upon admission to treatment.

      Depression and MA use are highly comorbid. The relationship between MA use and depression is
      likely bidirectional, with MA use causing changes in mood and being used as a self-medicating
      behavior to reduce symptoms of depression. Several studies have shown that depression rates
      are higher in MA-using females compared to their male counterparts. It is likely that
      neurobiological and psychosocial mechanisms contribute to increased incidence of depressive
      symptoms in females.

      No clear treatment model exists to suggest how the comorbidity of depression and MA use is
      best managed. In studies of antidepressants for treatment of MA withdrawal and dependence,
      findings have suggested that antidepressants are ineffective for treating depressive
      symptoms.

      Creatine is an organic acid occurring naturally in vertebrates, where it takes part in energy
      homeostasis in tissues with fluctuating energy demands. Exogenous creatine has been shown to
      increase brain concentrations of PCr. Neuroimaging studies of creatine have shown increased
      brain phosphocreatine (PCr) content with creatine administration. Therefore, we hypothesize
      that oral creatine administration will increase PCr levels and reduce depressive symptoms in
      a sample of depressed female MA users. This hypothesis will be tested by a within subjects
      design by giving depressed MA using females oral creatine for eight weeks and measuring PCr
      pre- and post-treatment with magnetic resonance spectroscopy. Moreover, depressive symptoms
      will be measured by administration of the Hamilton Depression Rating Scale twice weekly
      during the course of creatine treatment.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Female gender, ages 18-64 years inclusive

          2. Diagnosis of MA dependence or abuse within the past 12 months, with MA preferred drug
             of abuse, identified by the SCID-I-RV

          3. Current diagnosis of Major Depressive Disorder identified by the SCID-I-RV

          4. Current HAM-D17 score of > 15

        Exclusion Criteria:

          1. Diagnosis of bipolar disorder, schizophrenia, or schizoaffective disorder, identified
             by the SCID-I-RV

          2. History of or current diagnosis of renal disease, such as chronic renal failure, acute
             renal failure or end stage renal disease

          3. Diabetes type I or II

          4. Colitis or diverticulitis

          5. Seizure disorder

          6. Current serious suicide risk identified by the Columbia Severity Suicide Rating
             Severity

          7. Current treatment with an antipsychotic, mood stabilizer, or antidepressant

          8. Positive HIV test

          9. Active Hepatitis C

         10. Contraindication to magnetic resonance scan