Pharmacological Treatment of Substance Abuse

1. Pharmacological Treatment of Substance Abuse • What are your thoughts, in general, of pharmacological treatments for psychological disorders? • What might be some particular concerns regarding pharmacological treatments of substance abuse?

2. Pharmacological treatment exists for two main phases of addiction: • Management of withdrawal • Theoretically increases likelihood of initial abstinence • Relapse prevention • Four broad ways that a pharmacological treatment can work: • Agonist: directly binds (stimulates) receptor, provides similar effects as substance of addiction • Indirect agonist: stimulates neurotransmitters that are impacted by substance, but does not “replace” substance • For examples, activation of dopaminergic system • Partional agonist: binds to receptor, but effects not as powerful as agonist • Antagonist: binds to receptor and blocks effects of other substance • Strengths and weaknesses of each?

3. Nicotine • Although not a focus in this course, important because very popular form of psychopharmacology for addictive behaviors • Nicotine Replacement Therapy (NRT) • Alternative way of providing the body with nicotine • Alleviates withdrawal symptoms, for obvious reasons • Multiple ways that NRT can occur • Patch, gum, inhaler, spray, lozenge • For “the patch” one gets about half the nicotine one would from smoling

4. NRT is not intended to be long-term • For example, a typical patch treatment is 8 weeks • Success rates for patch seem to be about 30% (6 month follow-up) • Locally, many hospitals are no offering free NCT for patients and staff

5. Bupropion (e.g., Wellbutrin • Atypical antidepressant that blocks dopmaine and norephinephrine reuptake • Also seems to serve as an antagonist at the nicotinic acetylcholine receptor • Receptor that underlies reinforcing properties in the brain • Benefit of treating two disorders at once (dose is the same) • Nortriptyline may be a second line choice, but can result in some side effects

6. Pharmacological treatments likely more effective when combined with behavioral counseling • e.g., one study found quit rates for NRT gum jumped from appx. 10%-29% (Hall et al., 1990)

7. Alcohol • Initial pharmacotherapy involved benzodiazepines for alcohol withdrawal • Recall that alcohol withdrawal results in hyperactvity of the autonomous nervous system, anxiety, etc. • Disregulation occurs with alcohol abuse • Benzos help manage these symptoms • Only occurs for 3-4 days (potential for addiction) • Anticonvulsants can also be used for withdrawal • Disulfiram (e.g., Antabuse) • Provides an aversive reaction when someone drinks alcohol

8. Inhibits liver enzyme that breaks down acetaldehyde, the toxic substance that results from alcohol metabolism • Results in facial flushing, nausea, vomiting, etc. • Does NOT impact cravings • Client must be motivated, and compliance should be supervised • Naltrexone (e.g., Revia) • Opiod antagonist • Some of its effects are because of these properties

9. Acamprosate (Campral) • Reduces neuronal hyperexcitability during withdrawal • Not addicting, which gives it a benefit over benzodiazepines • May also be used in longer-term treatment (e.g., Project COMBINE) • SSRIs • Typically proscribed for depression (e.g., Prozac, Paxil, Zoloft) • A number of studies have examined their effectiveness, without promising results

10. Opiates • Most effective treatment involves agonist therapy (e.g., methadone) • Agonists are longer acting, less reinforcing, and (theoretically) eliminate dangerous drug seeking behavior • “Dangerous,” though, because one can OD on them • Generally, only used with “severe” cases (e.g., dependent for over a year) • Antagonists can also be prescribed (e.g., Naltrexone) • Patient should have already gone through detox • Problems in terms of patient retention

11. Naloxone is used to treat opioid intoxication • Physically displaces opioids from brain receptors • Clonidine (high blood pressure medicine) can be used in withdrawal

12. Pharmacological interventions have been tried for stimulants (e.g., cocaine, meth) and marijuana, with less than promising results • Disulfirm may have some effectiveness with cocaine • Some of its effect may be indirect

13. Other issues in pharmacotherapy • Combination pharmacotherapy • Most effective therapy might involve combining substances • For example, combination for both withdrawal and relapse prevention • Or, combination that addresses different rewarding aspects of the substance • Patient matching • Certain types of patients may do better with certain medications • For example, SSRIs may be effective with late-onset alcoholics, while naltrexone may be most effective with early-onset

14. Adherence • The best pharmacotherapy is useless without patient motivation • Adverse effects are important • Support and motivation are helpful

15. Project COMBINE • Huge trial funded by NIAAA • Participants were randomized to one of nine groups:

16. CBI only • CBI + Medication Management (MM)-placebo • CBI + MM-naltrexone • CBI + MM-acamprosate • CBI + MM-both • MM-placebo only • MM-naltrexone only • MM-acamprosate only • MM-both

17. Results of the study were modest, at best • Overall, participants reported increased percent days abstinent (25.2%-appx 65% at one-year follow-up) • For those not getting CBI, naltrexone was more effective than placebo • Those getting CBI alone (no MM) fared worst in-treatment (baseline to 16 weeks) • No real benefits of CBI + medication • No real benefits of acamprosate

18. Why such modest effects? • Lack of CBI standardization • Reactivity effects

19. Project MATCH • Controversy in psychotherapy treatment literature regarding “common” versus “specific” factors • Theory behind the MATCH study was that patients with certain types of characteristics would benefit from certain types of treatments

20. Study was conducted at 10 sites: 5 outpatient and 5 aftercare • Three different individual treatments: • CBT (12 sessions) • MET (4 sessions) • TSF (12 sessions) • Ten client “matching” characteristics: symptom severity, cognitive impairment, client conceptual level, gender, meaning seeking, readiness to change, psychiatric severity, social support, sociopathy, typology

21. Hypotheses were that these variables would interact with treatment condition (Table 1, p. 9) • Primary outcomes were percent days abstinent and drinks per drinking day • Participants were 952 outpatients and 774 aftercare patients (huge sample); • Mostly male • Most met dependence rather than abuse criteria • Data collected at baseline, 3-, 9-, and 15-month follow-ups (follow-ups appx. 90%)

22. Study Results: • Substantial positive changes across all treatments • PDA went from 20-25% to 80-90% (varied between aftercare and outpatient) • DDD went from 11-20 to 1-4 • Gains maintained across follow-up periods • Few main effects for treatment type, and those that emerged were modest and not stable (e.g., TSF patients had fewer alcohol-related problems at 9 months but not 15 months) • Note difference in length of sessions, though • Few of the matching hypotheses were supported

23. So, what are the implications of this study?

24. Substance Abuse Prevention and Treatment Overview (Martens et al., in press) • Broad review of intervention/prevention effectiveness • Different types of prevention: • Universal • Presented to all members of a target population • School setting is most popular • Selective • Presented to targeted members based on risk factors (e.g., Greek college students; low-income adolescents)

25. Indicated • Presented to those already experiencing problems • Prevention effectiveness • Knowledge-based universal programs not effective • Comprehensive life skills programs and system wide programs demonstrated moderate effects (universal) • Parenting programs may be particularly effective • Mass media prevention programs not generally effective • MI-based and alcohol skills training programs are effective in indicated and selective prevention settings

26. Treatment Effectiveness • MI, CBT, and TSF all have support, as do marital/family approaches • Contingency management approaches can be effective • Some studies have found that MI is as effective as other treatments with fewer sessions • Education only and confrontation consistently shown to be ineffective