Settembre-Ottobre 2018, Vol. 53, N. 5 Riv Psichiatr 2018;53(5):233-255 doi 10.1708/3000.30003 Scarica il PDF (264,0 kb) Psychosocial interventions in stimulant use disorders: a systematic review and qualitative synthesis of randomized controlled trials titolo - split_articolo,controlla_titolo - art_titolo Psychosocial interventions in stimulant use disorders: a systematic review and qualitative synthesis of randomized controlled trials title - controlla_titolo - art_title Interventi psicosociali nei disturbi da uso di psicostimolanti: una revisione sistematica e sintesi qualitativa di studi clinici randomizzati autori - vau_aut_id RICCARDO DE GIORGI1,2, CAROLINA CASSAR3, GIAN LORETO D’ALÒ4, MARCO CIABATTINI4, SILVIA MINOZZI5, ALEXIS ECONOMOU2, RENATA TAMBELLI3, FRANCO LUCCHESE3, ROSELLA SAULLE5, LAURA AMATO5, LUIGI JANIRI6, FRANCO DE CRESCENZO1,6 testo - art_testo *E-mail: firstname.lastname@example.org; **email@example.com affiliazione_autori - art_affiliazioni 1Department of Psychiatry, University of Oxford, Oxford, UK 2Oxford Health NHS Foundation Trust, Oxford, UK 3Department of Dynamic and Clinical Psychology, Sapienza University, Rome, Italy 4School of Hygiene and Preventive Medicine, University Tor Vergata, Rome, Italy 5Department of Epidemiology, Lazio Regional Health Service, Rome, Italy 6Institute of Psychiatry and Psychology, Fondazione Policlinico Universitario A. Gemelli, Università Cattolica del Sacro Cuore, Rome, Italy riassunto - art_riassunto SUMMARY. Stimulant use disorders are highly prevalent with a large burden of disease. Most clinical guidelines recommend psychosocial interventions, but there are no clear hierarchies or indications. Moreover, these interventions have been reported unevenly in the literature. Identifying the most suitable treatment for each patient therefore represents a major challenge. In this review, we describe all psychosocial interventions for stimulant use disorders investigated in randomized controlled trials – including contingency management, cognitive behavioral interventions, community reinforcement approach, 12-step program, meditation-based interventions and physical exercise, supportive expressive psychodynamic therapy, interpersonal psychotherapy, family therapy, motivational interviewing, drug counseling –, and we synthesize the main findings of these studies. Similarities and differences between treatments are highlighted, suggesting that distinct psychosocial interventions can be relevant for certain patients’ groups but not for others. Conversely, several interventions can be equally effective in similar clinical contexts, suggesting that a shared element such as therapeutic alliance is key. Finally, combined approaches emerge as a viable option for people with complex needs. Future studies will need to benchmark psychosocial interventions in stimulant use disorders and ascertain markers of response with a view to individualized treatment. parolechiave - lingua - vke_key_id KEY WORDS: Stimulant use disorders, psychosocial interventions, cocaine, systematic review, amphetamine. abstract - art_abstract RIASSUNTO. I disturbi da uso di stimolanti sono altamente prevalenti e hanno gravi ripercussioni nei pazienti a livello medico, psicologico e sociale. La maggior parte delle linee-guida cliniche raccomanda l’uso di interventi psicosociali per il trattamento, ma le indicazioni sono generiche e non si riferiscono a quali interventi psicosociali si debbano preferire. Inoltre, gli interventi sono stati riportati in modo non uniforme in letteratura. Identificare il trattamento più adatto da offrire per un singolo paziente rappresenta una grande sfida. In questa revisione sistematica, descriviamo tutti gli interventi psicosociali che sono stati studiati in studi clinici randomizzati per i disturbi da uso di psicostimolanti e sintetizziamo i principali risultati di questi studi. Evidenziamo anche le somiglianze e le differenze tra i trattamenti, suggerendo che distinti interventi psicosociali possono essere rilevanti per alcuni gruppi di pazienti ma non per altri. Al contrario, diversi interventi possono essere ugualmente efficaci in contesti clinici simili. Infine, gli approcci combinati emergono come un’opzione praticabile, soprattutto in caso di diagnosi doppia. Gli studi futuri dovranno valutare i marcatori di risposta in vista di un trattamento individualizzato. keyword - lingua - vke_key_id PAROLE CHIAVE: disturbi da uso di psicostimolanti, interventi psicosociali, cocaina, amfetamina, revisione sistematica. testo - art_testo INTRODUCTION Stimulants are a class of psychoactive substances that excite the nervous system through complex interactions with monoamine transporters and neurotransmitters1. Cocaine and amphetamines are the most commonly abused stimulants, with an annual prevalence of 0.38% and 1.20% respectively in those aged 15-64 years2. Stimulant use disorders are characterized by the sustained use of these substances leading to substantial impairment and distress3. Common symptoms include craving for stimulants, failure to control use, continued use despite interference with major obligations or social functioning, use of greater amount over time, development of tolerance, spending a great deal of time to obtain and use stimulants, and withdrawal symptoms that occur after stopping or reducing use. These patients are at increased mortality risk and suffer from several comorbidities including psychosis and other mental illnesses, neurological disorders, cardiovascular dysfunctions, sexually-transmitted diseases, and blood-borne viral infections 4. Moreover, the impact on society is large because of the association between stimulants use and offending5. Recent data suggest that people affected by stimulant use disorders are increasingly seeking out treatment2. Usually these patients do not require inpatient care because withdrawal syndromes are not severe or complex, and most can be safely treated in outpatient programs. Psychiatric and psychological management is advocated as the best evidence-based option for these patients and aims to: • motivate the patient to change; • establish and maintain a therapeutic alliance with the patient; • assess the patient’s safety and clinical status; • manage the patient’s intoxication and withdrawal state; • develop and facilitate the patient’s adherence to a treatment plan; • prevent the patient’s relapse; • educate the patient about substance use disorders; • reduce the morbidity and sequelae of substance use disorders. Clinical guidelines recommend psychosocial interventions as the treatments of choice for all stimulant use disorders6-9, and there is no evidence of differential effect for any psychosocial intervention in the management of patients using distinct stimulants10. The development and assessment of psychosocial interventions for substance use disorders has been a priority of the National Institute on Drug Abuse for over 20 years11. However, a key limitation of studies investigating psychosocial interventions is that even well designed randomized controlled trials are subject to biases that can falsely increase the likelihood of a positive outcome12-14. A recent systematic review and meta-analysis provided encouraging results on the efficacy and acceptability of all types of psychosocial interventions for stimulant use disorders15; however, this study did not compare qualitatively the various treatments. In this paper, we performed a systematic review and qualitative synthesis of all psychosocial interventions assessed in randomized controlled trials. Our aim is to provide clinicians with a comprehensive description of all the available psychosocial interventions for stimulant use disorders and report the most recent evidence-base for them. METHODS Literature search We performed an extensive computer literature search of peer-reviewed articles about psychosocial interventions in stimulant use disorders on the following databases: Cochrane Drugs and Alcohol Group Register of Trials, Medline, Embase, CINAHL, ISI Web of Science, PsycINFO. The search strategy is available as appendix 1 in the supplementary material. We added a hand-search of the reference list of retrieved articles. All searches included non-english literature. Study selection We included all randomized controlled trials comparing psychosocial interventions, either alone or in combination with pharmacological therapy, against no-treatment, waiting list, or any other psychosocial treatment. We only accepted studies performed in adults (>18 years old) with a diagnosis of stimulant use disorder according to the Diagnostic and Statistical Manual of Mental Disorders (DSM) -III, -IV or -5 or the International Classification of Diseases (ICD) -9 or -10. We excluded review articles, editorials, letters, comments, conference proceedings, case reports, and case series; studies dated before 1990 if the system used for the diagnosis did not use operationalized criteria, but only disease names with no diagnostic criteria (i.e. ICD-9); trials lacking a control group. Three authors (FDC, GLDA, MC) independently reviewed the titles and abstracts of the articles retrieved, applying the inclusion and exclusion criteria; then, they examined the full-texts to confirm the studies’ eligibility for inclusion. Disagreements were resolved by consensus. Data extraction We designed and used a structured template to ensure consistency and we systematically appraised each study. Data extracted embraced characteristics of the studies (i.e. first author, publication year, journal), of the participants (i.e. mean age, diagnosis), and of the interventions (i.e. types of treatment, comparisons, duration of treatment, duration of follow-up). Qualitative synthesis Two authors (CC, RDG) retrieved the manuals for each psychosocial intervention included and summarized the key principles. Then, they integrated these data with the main findings from all the randomized controlled trials previously selected. Risks of bias in the included studies were assessed using the tool described in the Cochrane Collaboration Handbook as a reference guide, which pays particular attention to random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective reporting 16. This tool allows a rating of “low”, “unclear” or “high” risk of bias. RESULTS Our computer-based search retrieved 6 728 records. After removing 2 660 duplicates, further 4 068 articles were excluded because they did not meet the required criteria, leaving 108 full-text articles included. Further six studies were added from trial registries and one additional article was retrieved from hand-search. A total of 115 articles corresponding to 91 randomized controlled trials (RCTs) were finally included in this review (see figure 1 in the supplementary material). The characteristics of the studies included is reported in Table 1, while in Table 2 we summarized the main differential elements of the psychosocial therapies included. A risk of bias summary is available as Table 3 in the supplementary material, while the references of all the included RCTs are listed in the Appendix 2 in the supplementary material. Overall, contingency management (CM) was investigated in 45/91 studies (49%), cognitive behavioral interventions in 32/91 studies (35%), community reinforcement approach (CRA) in 9/91 studies (10%), 12-step program (12SP) in 8/91 studies (9%), meditation-based interventions (MbI) and physical exercise (PhE) in 6/91 studies (7%), supportive expressive psychodynamic therapy (SEPT) in 3/91 studies (3%), interpersonal psychotherapy (IPT) in 3/91 studies (3%), family therapy (FT) in 3/91 studies (3%), motivational interviewing (MI) in 11/91 studies (12%), drug counselling (DC) in 10/91 studies (11%). It should be noted that some studies examined numerous or combined interventions at the same time (see Table 1). Contingency management (CM) Theoretical background Contingency management (CM) is a behavioral intervention that emphasizes the positive reinforcement of healthy behaviors, whereby addicted patients are incentivized with rewards for providing drug-free urine samples17. It differs from non-contingent reward where patients are remunerated irrespective of the results of the urine drugs screening. Similarly to drugs, CM applies positive reinforcers to abstinent behavior and immediately conveys relief and satisfaction. The purpose is to promote abstinence and improve the welfare of an often-deprived population. Trials A wealth of studies examined CM in stimulant use disorders. a) Cash rewards There is little research on CM using cash rewards, which showed that a cash-based CM combined with bupropion18 or topiramate19 improved outcomes in cocaine users compared to non-contingent rewards, regardless of the use of medication. b) Voucher rewards Since cash rewards may be spent on substances, most CM approaches offered vouchers instead. Voucher-CM was not inferior to cash-CM in improving cocaine abstinence and treatment attendance, regardless of the high or low value of the rewards20,21. Cocaine and crack cocaine users responded to voucher-based CM with increased acceptability and abstinence rates22 and reduced craving23. The use of CM coupons of escalating value was associated with sustained cocaine and opiate abstinence in a population of methadone-maintained patients24,25. Conversely, Rawson et al.26 and Menza et al.27 reported an improvement in short-term outcomes that was not maintained at follow-up, while Umbricht et al.28 did not show any difference in abstinence between voucher-based CM and non-contingent rewards. c) Prize rewards Stakeholders underlined that the cost of vouchers paid by the health system can be high on a large scale; therefore, another approach consisted of awarding prizes and lottery tickets attracting numerous low-value and limited high-value rewards. Petry et al.29 showed that voucher and prize CM were equally effective in cocaine-using methadone patients, and prize-based incentives improved abstinence outcomes30 and psychiatric comorbidities31,32. Low-cost prizes can increase abstinence33-35, but higher-magnitude prizes proved better on the long term36,37. Longer periods of prize-CM promoted longer durations of abstinence38 and increased post-exposure prophylaxis in men who have sex with men using methamphetamine39. However, some studies showed that prize-based CM did not significantly improved abstinence in stimulant use disorders, but it did in opioid40 and alcohol use41. d) Other rewards Addicted patients may struggle with failing the lottery draw or can be inadvertently fed into a gambling addiction; hence some alternative CM strategies were devised. In case of stimulant- and opioid-use comorbidity, buprenorphine doses were provided as CM rewards, resulting in increased abstinence at follow-up compared to CM vouchers42,43 used an employment-based reinforcement that proved effective in long-term abstinence, but another study showed low engagement with a similar approach44. Cognitive behavioral interventions Theoretical background Cognitive behavioral interventions are based on cognitivism and behaviorism paradigms. Cognitivism assumes that mental disorders are triggered by unhealthy beliefs45,46: thoughts such as “I need to escape”, “I cannot deal with this unless I am high”, and “I deserve to get high considering what I am going through” are commonly noted to precede stimulants use47. Behaviorism maintains that most human traits and actions are learned48, therefore stimulants use can be considered a learned behavior47. Cognitive behavioral interventions aim to modify cognitions and behaviors that lead to substance misuse. Trials in stimulant use disorders included cognitive behavioral therapy (CBT), gay-specific cognitive behavioral therapy (G-CBT), and relapse prevention (RP). a) Cognitive behavioural therapy (CBT) Theoretical background CBT for stimulant use disorders is a short-term psychotherapy divided into functional analysis and coping-skills training47. Functional analysis is based on the antecedents, behavior, and consequences model46. Initially, patient and therapist explore the features of historical drug use. They move next at analyzing maladaptive behavioral patterns including timing, frequency, and intensity of misuse, as well as any environmental, psychological, or somatic trigger for craving. Finally, emerging personal and interpersonal resources, motivation for change, and future goals are discussed. Coping-skills training works on basic learning mechanisms that led to stimulants use in the first place, such as modeling49,50, classical conditioning51, and operant conditioning52. Modeling theory suggests that people learn new behaviors by watching and then imitating others, so patients exposed to negative models of drug use within their family or peer group will shape their behavior accordingly and develop an addiction. On this basis, CBT aims to replace that negative model with a positive one conveyed by the therapist; also, new skills such as rejecting an offer of drugs and managing relationships with peer users are presented through role-play in a therapeutic setting and then routinely practiced by patients. Classical conditioning occurs when an unconditioned stimulus is paired with another conditioned stimulus, producing a conditioned response; thus, the recurrent use of stimulants (i.e. the unconditioned stimulus) can be associated with places, times, money, and other triggers (i.e. the conditioned stimuli) that will elicit craving for substances (i.e. the conditioned response). Here, CBT is used for increasing awareness of these unhelpful mechanisms and facilitate the avoidance of high-risk situations. Operant conditioning requires active involvement of the subject because future behavior relies on the consequences of past behavior; in stimulant use disorders, the intake of cocaine and amphetamines is reinforced by its most desired consequences such as increased energy and efficiency, euphoria, grandiosity, and disinhibition. A CBT approach encourages patients to examine the short- and long-term outcomes of stimulant use, which turn out to be negative in most cases (i.e. a negative reinforcement); moreover, the therapist can redirect patient’s behavior to other pleasant endeavors such as hobbies, work, and relationships (i.e. positive reinforcement). Trials Many trials assessed CBT in stimulant use disorders. CBT was associated with improved outcomes in cocaine53, crack cocaine54, and methadone-maintained cocaine users26 with lasting effects. Even non-intensive CBT delivered fortnightly over 12 weeks was effective in cocaine use55, and Baker et al.56,57 obtained comparable results with a brief CBT intervention plus psychoeducation via self-help booklets in amphetamine users. A CBT strategy focusing on the negative effects of misuse significantly reduced craving for the substance in methamphetamine58 and cocaine users59. Carroll47 and Carroll et al.11 showed that combined CBT and disulfiram was effective in cocaine use disorder irrespective of concurrent alcohol misuse. In contrast, one study reported that CBT was less effective than counseling in reducing days of cocaine use and drug-related problems60, whilst another compared CBT with other interventions, but no abstinence outcomes were reported for it61. As CBT can be resource-consuming, some researchers attempted strategies for increasing availability. Group CBT failed to show any difference against usual treatment62. A preliminary study by Keoleian et al.63 used a CBT-based text-messaging intervention for methamphetamine users that showed high feasibility and acceptability. Carroll et al.64, delivered a computer-based CBT to cocaine users on methadone, reporting easy accessibility and increased abstinence with lasting effects. Finally, another study used a self-guided web-based intervention based on CBT and motivational interviewing principles over 6 months via a free-to-access site for amphetamine users, but this failed to show improvement in drug use and engagement remained low65. b) Gay-specific cognitive behavioral therapy (G-CBT) Trials Cognitive behavioral interventions can be targeted to specific populations: G-CBT was adapted for men who have sex with men affected by methamphetamine dependence by Shoptaw et al.66,67. In addition to standard cognitive-behavioral principles, G-CBT considered cultural aspects of methamphetamine use by men who have sex with men including triggers such as circuit parties and sex clubs, and obtained significant and sustained improvements in both drug use and prevention of HIV. c) Relapse prevention (RP) Theoretical background Once abstinence is achieved, cognitive behavioral interventions aim to prevent further relapses. The RP model views relapse as secondary to difficulty in coping with immediate determinants (i.e. negative emotional states, relational problems, social pressures, lapses) and to covert antecedents (i.e. life-style, urges and craving)68. Through RP work, patients learn to identify high-risk situations such as lapses that are associated with guilt and other negative emotions, eventually leading to relapses. Lapse management uses cognitive restructuring to recognize lapses and relapses not as failures but opportunities to learn from mistakes. RP interventions also focus on the antecedents and aim to reduce stressful life-style factors by eliminating all items associated with stimulants use and promoting “positive addictions” such as meditation, relaxation training, and other recreational activities. Trials RP reduced cocaine and other drugs use post-treatment69, and it was more effective in those whose drug use was the most severe70-72. Group and individual approaches showed comparable results73. However, McKay et al.74 stressed that RP was useful only after abstinence was fully achieved. d) Cognitive behavioural interventions plus CM Trials Cognitive behavioral interventions are often combined with CM with a view of increasing the engagement with therapy. CBT plus CM increased abstinence in cocaine users75, especially when rewards were arranged in conjunction with therapeutic progress76. Also, combining RP with CM improved outcomes in cocaine users who had achieved initial abstinence77. Rawson et al.26,78 reported superior short- and long-term outcomes for CBT and CM respectively, but no additive effect was observed. On the contrary, combined CBT and CM obtained significantly better outcomes than CBT or CM alone in cocaine79,80 and methamphetamine users67. Milby et al.81 studied a population of homeless cocaine users and showed that the combination of a housing- and employment-based CM with cognitive behavioral interventions lead to more durable abstinence. A preliminary study by Carrico et al.82 highlighted the feasibility of CBT plus CM in a high-risk population of Cambodian female sex workers using amphetamines who live in a resource-limited area. Community reinforcement approach (CRA) Theoretical background The community reinforcement approach (CRA) is a multilayered intensive intervention delivered over 24 weeks and adapted to treat cocaine and amphetamines addiction83. It teaches drug avoidance skills, encourages lifestyle changes, gives relationship counseling, and addresses comorbid substance use and psychiatric disorders. As in CBT, it involves functional analysis and coping-skills training. Social, familial, recreational, and vocational reinforcers are largely used, providing a comprehensive and supportive structure to treatment. a) CRA alone Trials Only one trial used CRA alone, showing better retention and abstinence rates, and improvements in addiction severity scores after 24 weeks of treatment84. b) CRA plus CM Trials Incentives such as vouchers and out-of-treatment sessions (e.g. meetings outside the office hours) are frequently added to improve treatment compliance. Numerous studies by Higgins et al.17,85-87, García-Rodríguez et al.88, García-Fernández et al.89,90 showed that CRA plus CM was effective, had increased retention rates, and improved psychosocial outcomes in cocaine users, although this was not demonstrated at follow-ups longer than 6-12 months after the end of treatment. These findings were confirmed in cocaine users of any socioeconomic status91. However, another study failed to show any superiority of CRA when added to CM92. 12-step program (12-SP) Theoretical background The 12-step program (12-SP) was originally designed for alcoholism93 and then adjusted to several other substance use disorders including cocaine and amphetamines. Contrarily to other treatments, it considers addiction as a chronic illness that can be controlled, but never cured. It is largely based on spiritual and relational principles applied to a fellowship of peers associated by the willingness to fight addiction. All members share a transcendent yet pragmatic vision embraced in twelve steps (see box 1 in the supplementary material), including the acceptance of being addicted and the surrender to a “higher Power”, often but not necessarily interpreted as God. The self-help group reduces social isolation and conveys support and empathy from people facing similar problems, all in complete anonymity. However, complex group dynamics pose frequent challenges, especially because most members are not trained to work on this aspect. Moreover, group therapies normally do not allow enough time to address deeper individual experiences. A 12-step facilitation therapy was therefore developed with the aim to improve participation and involvement in the 12-SP 94. This is a structured, individual, and time-limited intervention delivered by a trained psychotherapist. a) 12-SP alone Trials Trials of 12-SP and 12-step facilitation in stimulant use disorders achieved modest95 or mixed96 results. Two studies showed that 12-SP and cognitive behavioral interventions were equally effective in patients addicted to cocaine and alcohol69,97. Maude-Griffin et al.54 obtained opposite results but highlighted a potential benefit from 12-SP in the specific subgroup of African American with strong religious beliefs. b) 12-SP plus other interventions Trials Few studies on combined interventions are reported in literature. The effectiveness of 12-SP plus counseling in cocaine use disorder was supported by Weiss et al.61, who reported that active participation predicted less cocaine use. Higgins et al.85 compared 12-SP plus non-contingent reward with CRA plus CM, but the former resulted in worse outcomes. However, when CM was combined with either 12-SP or CRA, no difference between treatments was found92. Meditation-based interventions (MbI) and physical exercise (PhE) Meditation-based interventions (MbI) and physical exercise (PhE) share several theoretical underpinnings and therefore are reported together. a) Meditation-based interventions (MbI) Theoretical background Meditation refers to a broad variety of practices including body scan, yoga, and mindfulness meditation, whereby individuals train their minds to pay greater attention to internal and external experiences as they occur98,99. It is not designed to suppress dysfunctional behaviors, but encourages the adoption of a non-judgmental approach to stressful experiences, leading to detachment and lower reactivity to stimuli associated with relapse and reduced distress. It can be delivered in group and then self-applied, so the overall cost is low. The engagement with MbI can vary as some patients may have a positive attitude towards it, but others may be reluctant to abandon traditional talking-based therapies. Trials MbI for stimulant use disorders were examined in 3 trials. Smout et al.100 devised a modified version of the acceptance and commitment therapy101,102, integrating aspects of mindfulness training and behavioral therapy and consisting of weekly 60-minute individual sessions for 12 weeks. This was tested on a sample of methamphetamine users and showed results comparable to those of a CBT intervention of the same intensity. Chen et al.103 used a different MbI to treat cocaine addiction, which involved adjusting the breath to near-resonant frequency, regulating the mind with inward attention and guided imagery, and ear acupressure. This treatment was confirmed to increase abstinence and to reduce craving and anxiety when compared to usual treatment. Yoga meditation was used on a population of crack cocaine users with comorbid HIV, showing high feasibility and acceptability as well as modest improvements in measures of quality of life 104. Finally, a recent trial developed a Mindfulness Based Relapse Prevention and used it in addition to CM for patients with stimulant use disorders, showing declining stimulant use among those with comorbid depressive and anxiety disorders105. b) Physical exercise (PhE) Theoretical background PhE is an intervention that is thought to impact directly on stimulant use and mediates important health-related outcomes such as withdrawal symptoms, mood, sleep, cognitive function, and quality of life106. Trials A few studies recently assessed various PhE interventions in stimulant use disorders. Zhu et al.107 used tai-chi, a traditional Chinese sport classified as a moderate exercise, on amphetamine users, reporting significant improvements on all domains of a quality of life for drug addiction questionnaire. Rawson et al.108 showed that a structured PhE program and health education for methamphetamine users decreased substance use among lower severity patients and significantly reduced comorbid depressive symptoms. However, walking and running, in addition to a baseline intervention of CBT and rewards including cash and sport equipment, improved the fitness of cigarette-smoker patients with concurrent cocaine use disorder, but did not significantly improved abstinence and craving from cocaine 109. Likewise, a recent study failed to show any significant difference in abstinence rates between PhE and health education110. Supportive-expressive psychodynamic therapy (SEPT) Theoretical background All psychodynamic approaches derive from Freud’s psychoanalytic model; amongst these, supportive-expressive psychodynamic therapy (SEPT) is the only evidence-based for stimulant use disorders111. This psychotherapy was adapted for cocaine misuse by Mark and Luborsky112. It uses a “core conflictive relationship theme” based on the patients’ hopes and needs from relationships (i.e. wish), the reactions elicited from others and their experience of them (i.e. response from others), and their own reactions to the latter (i.e. response from self). According to this model, people who misuse cocaine often are or anticipate being criticized, rejected, mistreated, controlled, and humiliated (response from others). Consequently, they feel ashamed, guilty, helpless, suspicious, and angry (response from self). Cocaine is used as a means for regulating their pain, but this makes their targets (wish) difficult to recognize because of the effects of addiction. They refuse to take responsibility for their negative actions and are unable to consider the needs of others, which further reinforces cocaine use. The therapist supports the patient in viewing this aspect as another response from self and promotes the expression of deeper wishes such as being accepted, understood, loved, and independent. Patients become progressively more conscious of the three components of the core conflictive relationship theme, whereby they appreciate how their past and present relationships are linked to their cravings and relapses. As in all psychodynamic therapies, the analysis of transference and countertransference is framed within the approach. Trials Trials on SEPT for stimulant use disorders are scarce and only addressed cocaine misuse. A multimodal intervention based on the principles above determined significant improvements in drug use and psychological functioning113. However, another study reported worse outcomes for cocaine users treated with SEPT compared to counseling60 although a following analysis suggested that SEPT can be particularly effective to those patients who can achieve initial abstinence. Weiss et al.61 described the use of SEPT amongst other interventions, but no results about this therapy were reported. Interpersonal psychotherapy (IPT) Theoretical background Interpersonal psychotherapy (IPT) maintains that psychiatric disorders are caused and sustained by disturbances in interpersonal functioning114. Rounsaville et al.115 adapted IPT for ambulatory cocaine users and set two goals for therapy: reduction or cessation of cocaine use, and improvement in interpersonal functioning. Initially, patient and therapist agree a contract where the former recognizes the necessity of abstinence and abandons any ambivalence about the substance, whilst the latter can support in decision-making by comparing the negative and positive effects of drug misuse. Patients are prompted to recreate those thoughts and emotions preceding cocaine use and discuss strategies for managing their impulsiveness and avoiding social contexts that can be triggers. Attendance to self-help groups is encouraged to replace the addiction to drugs with engagement in group relationships. Usually, further work is required to achieve better interpersonal relationships, because patients often see drugs as having an important role in navigating interpersonal problems; for instance, cocaine is used when facing disputes, transitions, shortfalls, and grieves and to become more sociable, friendly, self-confident, and sexually disinhibited. Therapist and patient investigate these issues and try to identify alternative coping mechanisms instead of cocaine use. IPT is often considered a comprehensive approach to substance use disorders because it focuses on both drug misuse and interpersonal functioning; however, if the misuse is not directly linked to interpersonal problems, the applicability of IPT is poor. Trials Only 2 studies tested IPT in cocaine use disorder. Carroll et al.70 delivered weekly IPT sessions of 50-60 minutes for 12 weeks and reported significantly improved abstinence compared to CBT in the most severe users. However, a following trial by the same authors disconfirmed this result11. Family Therapy (FT) Theoretical background Family therapy (FT) poses emphasis on the relationships within the family system, including those who live in the household or are closely related, rather than the drug or the individual patient116. Firstly, addiction is reviewed in the context of the current family situation; for instance, an adolescent using cocaine can shift parental attention from a latent marital conflict to his drug problem, therefore preserving a degree of stability in the family. This assumes that family systems naturally reach a homeostatic state that may inadvertently maintain maladaptive patterns of behavior. The patient’s self and family blend in, producing separation anxiety and fear to grow, so that the whole family system is trapped at a developmental stage. The therapist’s task is to stimulate a restructuring of the system to maximize the potential of each family member. Enmeshment and disengagement are additional therapeutic avenues where family members can establish or loosen boundaries as appropriate 117. Patients are encouraged to draw a genogram of their family history for at least three previous generations; then, they are supported to identify recurrent maladaptive family patterns and develop an understanding of how these can be linked to their behavior, including drug misuse118. Trials There are few trials using FT specifically in stimulant use disorders. Hoffman et al.119 included an unstructured supportive FT in their study, where they combined several psychosocial interventions for treating a sample of cocaine users; however, no specific data for each treatment were provided. Kang et al.120 used weekly sessions of FT in a similar population, but no beneficial effect was observed. Both Hoffman et al.119 and Kang et al.120 used an unstructured supportive type of FT. On the contrary, Slesnick and Zhang121 developed a more structured ecologically-based FT (EBFT), which is a 12-session family system therapy, based on a social ecological theoretical perspective122. Slesnick and Zhang121 showed that EBFT is associated with a quicker decline in cocaine use in mothers using substances. Motivational interviewing (MI) Theoretical background Motivational interviewing (MI) is an evolution of Rogers’ person-centered counseling123 integrated with cognitive and behavioral strategies124, which argues that poor motivation and resistance contribute significantly to adverse outcomes in drug users. MI is a brief intervention, usually delivered in 2-4 sessions, aiming to manage the patient’s ambivalence about change through reflective listening, understanding, and empathy. Contrarily to other cognitive behavioral interventions, direct challenging is avoided as it could elicit defiance at this stage. Instead, discrepancies between the patients’ situation and their hopes for the future are highlighted, leading to a constructive discussion where the therapist shows patience and optimism and provides constant support in self-efficacy. Eventually, patients become more capable of identifying and enhance their motivation and readiness to change. a) MI alone Trials There are several studies on MI for stimulant use disorders. Two articles reported that a single session of MI, either alone or in combination with written health risk information, did not prove beneficial in respectively crack cocaine users on methadone maintenance125 and in a heterogeneous population of stimulant users126. Stein et al.127 compared 4-session MI to an assessment control and concluded that the former was better at reducing days of cocaine use amongst the heaviest community-based users. Polcin et al.128 delivered an unusually intensive 9-session intervention to patients with methamphetamine dependence, reporting a reduction in drug use and alleviated co-occurring psychiatric problems. Computerized versus in-person MI were compared with a view of further increasing the availability of this brief intervention, but no reduction in stimulants use was elicited regardless of treatment129. b) MI plus other interventions Trials MI is frequently combined with other brief interventions. Srisurapanont et al.130 assessed MI and health education in young students with methamphetamine dependence, reporting short-term benefits such as fewer days of drug use. The same combination was also trialed in a sample of crack cocaine users with comorbid HIV and poor adherence to antiretroviral therapy, showing improved compliance with treatment and fewer drug problems131. A single 50-minute session known as motivational enhancement therapy132 combining MI with personalized feedback about a preliminary assessment and health education, showed improved outcomes when used on ecstasy users133. Gonçalves et al.134 integrated MI with chess playing and showed that this can be an effective intervention in improving executive functions, associated with abstinence outcomes, in a population of cocaine users. Other 2 studies combined brief CBT with MI respectively for cocaine and amphetamine users, but results on abstinence outcomes were either inconclusive135 or not reported136. Drug counseling (DC) Theoretical background Individual drug counseling (IDC) for stimulant use disorders is largely inspired by 12-SP principles, seeing addiction as a disease damaging the person physically, mentally, and spiritually137. It is a semi-structured, time-limited intervention of 36 sessions over 6 months, which focuses on the present and sets short-term goals. Initially, patients need to accept having an addiction, seeing this as a disease, and aiming to abstinence. Then, they learn to recognize and avoid triggers, develop new coping strategies, and use objective measures of abstinence such as urinalysis. Finally, the counselor supports them to enhance their motivation and promotes lifestyle changes to prevent relapse and maintain recovery as a lifelong process. Drug counseling can also be delivered in groups (GDC) and it usually involves two phases 138. The first 12 sessions consist of a structured psychoeducational group to improve knowledge about addiction and learn about the recovery process; a second phase between sessions 12-36 educates on problem-solving techniques. As for any group therapy, it should offer a warm atmosphere, where each member can express opinions, problems, feelings and support; however, domination by an individual or isolation are common pitfalls. Both IDC and GDC usually encourage additional participation to 12-SP groups such as cocaine or amphetamine anonymous. Trials IDC and GDC are very commonly used in stimulant use disorders, although many available trials employed it as a baseline intervention29,54 or in conjunction with several other treatments139 without providing specific outcomes data. Gottheil et al.140 compared IDC, IDC plus GDC, and an intensive outpatient program for cocaine users, reporting improvements in drug use and severity of associated problems for all three interventions with no significant differences between treatments. Crits-Christoph et al.60 showed that a combination of intensive IDC and GDC was superior to psychodynamic and cognitive behavioral approaches in reducing days of cocaine use and drug-related problems. Weiss et al.61 reported that IDC was beneficial in cocaine users both in improving drug outcomes and in promoting participation to 12-SP sessions. Rawson et al.141 used a complex and intensive “matrix model” that combined 4 sessions of IDC, 16 weeks of twice-weekly group CBT, 12 sessions of family education groups, 4 sessions of social support groups, encouragement to attend 12-SP, and weekly testing for alcohol and stimulants on a large sample of methamphetamine users, showing significant improvements during the treatment phase that were not maintained on the longer-term. Other studies used telephone monitoring and adaptive counseling on cocaine users and showed that, when vouchers are used as rewards, engagement with therapy increased and abstinence outcomes improved 141-143. DISCUSSION AND CONCLUSIONS In this article, we systematically reviewed and qualitatively synthesized all psychosocial interventions studied in randomized controlled trials. Currently, this is the most complete review available on this subject. There are several theoretical differences between therapies. Cognitive and behavioral models predominate in randomized controlled trials, possibly because they are more likely to rely on standardized delivery protocols. CM, cognitive behavioral interventions, and CRA see addiction as deriving from dysfunctional thoughts and maladaptive learned behaviors, which they aim to modify through cognitive and behavioral techniques such as functional analysis, coping-skills training, and operant conditioning, with or without the addition of social support. The 12-SP acknowledges these issues, though does not address them in a systematic fashion, but adds a spiritual element that promotes acceptance of the disease. Similarly, MbI and PhE include practices focusing on understanding, modulating, and exerting inner bodily and spiritual energies and external experiences as a mean to reach acceptance and change. Relationships are central to the formulation of stimulant use disorders for SEPT, IPT, and FT, which differ because of their emphasis on the study of transference and countertransference, interpersonal functioning, and family systems respectively. Finally, MI and DC are classic counseling approaches because they refuse to assign a “sick role”, encouraging the development of immediate modifications of attitude and behavior. Moreover, practical differences can affect the choice of treatment. Some therapies are manualized and consistently available in the public health sector or via charities (e.g. CBT, 12-SP), whereas others are based on common theoretical principles but are not standardized (e.g. RP, SEPT), and therefore it is difficult to produce evidence to promote their diffusion. Clinicians and patients should discuss the pragmatic aspects of treatment delivery beforehand, because psychosocial interventions may vary in terms of intensity (e.g. low in DC, high in cognitive behavioral interventions), duration (e.g. brief in cognitive behavioral interventions, extended in SEPT and DC, lifelong in 12-SP), modality (e.g. IDC vs GDC or 12-SP), and media (e.g. face-to-face in most psychotherapies, very limited contact in CM, online or telephone in DC). The group of patients suffering from stimulant use disorders is heterogeneous. Several authors highlighted how specific psychosocial interventions may work best for particular subgroups of stimulant users or for a particular phase of the disorder, and indeed empirical research suggested that psychosocial treatment should be tailored to patients’ individuality and context144,145. Further research should address the need for more precise treatments, whereby evidence-based interventions can be personalized to the individual characteristics of people misusing substances146. In the absence of reliable predictors of response to different therapies, a better understanding of the underpinnings of psychosocial interventions in stimulant use disorders will aid clinical judgment. Likewise, interventions for stimulant use disorders are diverse, but they generally involve a therapeutic relationship between patient and therapist, with CM being the only exception. Considering all the theoretical and practical differences between psychosocial interventions, the “equivalence paradox” argues that a shared therapeutic alliance is essential for successful treatment of mental illness147, a concept which could hold true for stimulant use disorders. Some studies tested a range of combined treatments and there is evidence that the combination of diverse approaches, especially CM with other interventions, is feasible and leads to better outcomes in patients with several needs148. This review provide clarity around the similarities and differences between psychosocial interventions and therefore represent a useful framework for clinicians to conceive combined interventions that are clinically meaningful and likely to provide additive or synergistic effects. This review has several limitations. We only included psychosocial interventions investigated in randomized controlled trials leading to published articles, so it is conceivable that some treatments are not reported because no randomized controlled trials assessed them or, if so, they were not published. 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