Drug addiction substance use disorder Diagnosis and treatment

Mirtazapine is an antidepressant with a relatively good tolerance and safety profile. Food and Drug Administration and is commonly used to treat moderate to severe depression. Mirtazapine is a tetracyclic piperazinoazepine that enhances central noradrenergic and serotonergic activity by blocking alpha2 receptors and selectively antagonizing 5HT2 and 5HT3 receptors (De Boer 1996). Mirtazapine has also shown to improve suicidal ideation, to show relatively few side effects, and to show little abuse potential. The results of this review suggest that amineptine has some limited benefits in increasing the adherence to treatment and improving general condition but has no direct benefit on specific amphetamine withdrawal symptoms or craving.

PHARMACOLOGY OF METHAMPHETAMINE

Individuals suffering from CUD present with compulsive cocaine use patterns, strong cocaine craving, and high rates of relapse even after prolonged time of abstinence 2. Currently, there is no FDA-approved pharmacotherapy for CUD and treatment is mainly focused on symptom reduction 3. Neurobiological alterations in the brain are assumed to contribute to the observed clinical symptoms in CUD 4. This is supported by neuroimaging studies that have shown profound structural and functional alterations in the brain in individuals with CUD 5, 6. In addition to striatal brain regions involved in reward processing 7, frontal cortical areas that are neuroanatomically connected with limbic structures, are implicated in addiction due to their importance for inhibitory control 5, 6, 8.

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• Cocaine and amphetamines are the most commonly abused stimulants in people aged 15–64 years, with an annual prevalence of misuse of 0.38% and 1.20%, respectively 2.
• Different treatment options may be indicated for various degrees of severity of disorder.
• For abstinence, urine drug screens (UDS) were used 41 times (80%) and analysed or defined in 16 different ways.
• Like treatment for other chronic diseases such as heart disease or asthma, addiction treatment is not a cure, but a way of managing the condition.
• Amphetamines can make people feel more alert, and are prescribed for problems like depression and attention deficit order.

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• To our knowledge, only one clinical trial has addressed the treatment of MUD with comorbid opioid use disorder (OUD) 121.
• However, it’s important to note that for prescription medications taken as directed by a doctor, developing tolerance or dependence does not necessarily indicate a SUD and would not be counted among the 2 required criteria.
• However, meth has a high potential for abuse, which can mean dangerous and fatal consequences.
• Furthermore, presence of the study drug/metabolite does not necessarily indicate adherent consumption of the study drug, and authors varied in their assessments in that regard (i.e. present or not versus present at a defined level).
• We also calculated the number needed to treat (NNT), which is the number of patients that need to be treated in order for 1 to benefit from the intervention compared with TAU.

Characteristics of studies

Despite the differences in experimental design, of the 27 studies on CM effectiveness in MUD, only one found that CM did not effectively reduce METH use 81. Interestingly, evaluation of CM effectiveness in combination with another treatment (CBT e.g. 82, 83, nurse case management e.g. 84, pharmacotherapy 85, strengths-based case management e.g. 86 or a positive affect intervention e.g. 87) found no synergistic or additive effects. Nevertheless, there is evidence for CM decreasing METH use months post-treatment 88. Some comparisons were appraised as having low or very low quality, potentially restricting the validity of those results. All RCTs of psychosocial interventions for cocaine and/or amphetamine addiction are not blinded, which increases the risk of performance bias for self-reported outcomes. For this reason, we only reported data based on objective outcomes (abstinence on urinalysis and data on attrition), which are less likely to be influenced by the lack of blinding.

Chronic amphetamine abusers seeking treatment must successfully resolve amphetamine withdrawal when establishing sustained abstinence from the drug. It remains unknown whether improved outcomes in successfully resolving amphetamine withdrawal would also correspond with longer term abstinence outcomes. For subjective outcomes (global state, craving, and withdrawal symptoms), blindness of participants, personnel, and outcome assessors were conducted in only one study and was determined to be at low risk of bias.

This medication and others are currently in clinical trials, while new compounds are being developed and studied in preclinical models. Of the four studies that met the inclusion criteria, two studies compared amineptine with placebo (Jittiwutikan 1997; Srisurapanont 1999b) and two studies compared mirtazapine with placebo (Kongsakon 2005; Cruickshank 2008). Amineptine is an atypical tricyclic antidepressant that selectively inhibits the reuptake of dopamine and norepinephrine. Because amineptine has similar mechanism of actions as amphetamines, it was put forth that amineptine could help to relieve amphetamine withdrawal symptoms. Mirtazapine, a noradrenergic and specific serotonergic antidepressant, was also hypothesized to help reduce methamphetamine withdrawal severity by Amphetamine Addiction blocking the presynaptic alpha‐2 adrenergic receptors that inhibit the release of norepinephrine and serotonin.

We excluded studies on occasional users not actively seeking treatment and RCTs with study duration less than 4 weeks. We did not exclude studies on individuals with a comorbid substance use disorder (including opioid, alcohol, or cannabis use) or with a comorbid psychiatric disorder. Symptoms of amphetamine withdrawal during the initial days of abstinence from chronic amphetamine use can prompt individuals to return to regular drug use.

The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-V) criteria for Stimulant Use Disorder (SUD) and Stimulant Withdrawal 6 are listed in Table 1. In the previous version of the DSM (DSM-IV) 7, the classification listed ‘dependence’ rather than ‘use disorder’; with ‘moderate to severe’ SUD being regarded as equivalent to ‘dependence’. The International Classification of Diseases (ICD) 10th Revision (ICD-10) recognises ‘stimulant dependence syndrome’ and ‘stimulant withdrawal state’ 8. However, neither diagnostic tool differentiates between AMPH/MA and other non-cocaine stimulant SUDs; while the 11th Revision of the ICD narrows the definition to “stimulant dependence including amphetamines, methamphetamine or methcathinone” 9. In this paper, we have reviewed articles using all of the above classifications and sometimes interchangeably and our search included both terms. Most reviewed articles had eligibility criteria that included either the DSM-IV or DSM-V diagnostic criteria, and so we have combined the terms as dependence/use disorder.

• The chronic nature of addiction means that for some people relapse, or a return to drug use after an attempt to stop, can be part of the process, but newer treatments are designed to help with relapse prevention.
• Humans can binge on METH from 3 to 14 days 27, 28 (over 4 days/week of use on average).
• One study was judged to be at low risk of bias and three studies were judged to be at unclear risk of bias.
• METH and other drugs of abuse themselves are far too small to be immunogenic; therefore, the first step in active METH immunotherapies is creating a hapten molecule, a chemical derivative of METH, and linking it to immunogenic carrier protein 124.
• SAMHSA’s mission is to lead public health and service delivery efforts that promote mental health, prevent substance misuse, and provide treatments and supports to foster recovery while ensuring equitable access and better outcomes.

Characteristics of excluded studies ordered by study ID

Development of one or more medications for amphetamine withdrawal, particularly if implemented with evidence‐based behavioral or counselling interventions, would have great public health significance. Maintaining a review of outcomes from experiences using medications in clinical trials for amphetamine withdrawal is an important method for clinicians to stay current and to seek guidance regarding medication strategies when treating individuals in acute withdrawal from amphetamines. The primary interventions with evidence of efficacy in reducing METH use are behavioral therapies. The CM method has been most widely studied in subjects with MUD and overall demonstrated better outcomes than other behavioral therapies. Despite its effectiveness as a therapy for MUD, CM is not widely used, stemming in part from a policy limiting the monetary value of incentives allowable as part of treatment. Utilization of other behavioral treatments is also limited because they require substantial investments in care delivery systems.

Long-Term Effects of Meth Use

Passive METH immunotherapy involves vaccination with a pre-produced high affinity monoclonal antibody designed to bind to METH in a bloodstream following METH administration. Active METH immunotherapy involves vaccination with an immunogenic METH-containing conjugate which is able to stimulating specific antibodies capable of sequestering METH in the periphery 124. Reduction of METH entering the brain diminishes its reinforcing effects, thus reducing METH use and relapse 125. Several factors appear to predict CM treatment outcome, including problem severity, race, HIV status, education, and income 76. For example, CM therapy was the least effective for participants who reported a long history of drug use 89 or more METH use during baseline 86, and it was the most effective in Caucasian participants 88, 89.