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PHARMACOLOGY OF ADDICTIONS September 2015 Understanding the pharmacological basis of medications used to manage dependence Understanding how pharmacological agents are used to treat dependence Understanding that different medications are needed in the different phases of addiction Describing the medications commonly prescribed in dependence Substance dependence encompasses physical and psychological problems Physical dependence: on cessation of a drug to which the body has become adjusted, withdrawal symptoms occur. This can be life-threatening Psychological dependence: emotional and mental preoccupation with substances and craving Treat emergencies: overdose, seizures, dehydration, hypothermia/hyperthermia, acute confusional state, delirium tremens Treat detoxification and withdrawal syndromes: diazepam, chlordiazepoxide, lofexidine, methadone, buprenorphine Substitution: methadone, buprenorphine, nicotine replacement therapy, bupropion Relapse prevention: naltrexone, acamprosate, disulfiram Treatment of vitamin deficiency Treatment of comorbid psychiatric and physical disorders Patients should have the opportunity to make informed decisions about their care in partnership with professionals Special groups will need their treatment managed appropriately eg older and younger people will need lower doses and account needs to be taken of comorbid illnesses in older people Psychosocial interventions must be part of the package A full detailed assessment, including blood, urine, saliva investigations to ensure that substances have been used, has to be made before decisions about pharmacological treatment can be made Observations of withdrawal should be elicited if possible Antagonists at post synaptic receptor ie block synaptic transmission eg naltrexone Agonists have strong or 100% action on the receptor eg methadone Partial agonists induce less effect ie less than 100% eg buprenorphine Partial agonists will act like an antagonist if there is a full agonist present Methadone: long acting, half life 24 hours, can be used once a day Can be reduced slowly over weeks, has less euphoria than heroin Side effects: lethargy, respiratory depression at high doses especially with alcohol and benzodiazepines, constipation, reduced saliva (contributing to poor dental hygiene) Buprenorphine: partial agonist, long half life, administered once daily Attenuates the effects of opiates Produces less sedation, less euphoria and positive reinforcement, less respiratory depression Naltrexone: used when patient is abstinent; blocks the effects of heroin or opiate agonists and prevents reinforcing effects. Naloxone is a short acting opiate antagonist used in emergencies Lofexidine: adjunctive medication which reduces withdrawal symptoms Adjunctive medication i.e. anti inflammatory, anti-emetics, anti- depressants should only be prescribed at the lowest effective dosage, when clinically indicated ie when specific symptoms are present, and risk interactions should be considered Benzodiazepines: Reduce symptoms of withdrawal Reduce occurrence of delirium tremens Reduce seizures Disulfiram: used when patient is abstinent. Acts by inhibition of acetaldehyde dehydrogenase with leads to accumulation of acetaldehyde which interacts with alcohol to produce nausea, vomiting, headache, flushing, palpitations and hypotension, which can lead to collapse and death Acamprosate: commences once patient is abstinent and can improve rates of abstinence. It is hypothesised to reduce craving and urge to drink Naltrexone: better than placebo at reducing risk of lapse Nicotine Nicotine gum or patches, bupropion, varenicline E-cigarettes Stimulant No agents have been found to be useful Cannabis: No pharmacological agents have been shown to be helpful, but MET, CBT, CM have shown benefits Rarely present with dependence Rarely require substitute medication Most pharmacological preparations are not licensed for adolescents Initiation should be offered by a specialist addiction psychiatrists or specially qualified doctors Sometimes they require symptomatic medication Non-pharmacological interventions should be part of the treatment whether pharmacological treatments are being administered Require dosage reduction and careful monitoring Needs to take account of comorbid mental and physical health problems e.g. neuropsychiatric disorders, hepatic and respiratory complications Need to take account of other medications prescribed and the interactions with medications for substance use disorders Should be undertaken with the expertise of professionals trained in geriatric medicine, addiction psychiatry, old age psychiatry Initiation of detoxification and reduction regimes should be undertaken by the advice of specialists in addiction Particular caution should be taken with acamprosate, disulfiram, naltrexone Pharmacological treatment is one part of an integrated coordinated treatment plan A range of professional staff are involved in providing different components Coordination is necessary so that patients do not seek medication from different GPs, doctors and hospitals Pharmacists should be included in the multidisciplinary team to discuss issues e.g. choice of treatment, initi ation of medication, dosing regime, interactions with other medications Crome I.B (2009) Substance misuse and addiction in adolescence – issues for the practising GP in Care of Children and young people for the MRCGP (ed K.Mohanna). London. Royal College of General Practitioners. Department of Health (2007) Drug misuse and dependence – guidelines on clinical management: http://www.nta.nhs.uk/guidelines.aspx Lingford-Hughes, A. R., Welch, S., Peters, L and Nutt, D. J., with expert reviewers Ball, D., Buntwal, N., Chick, J., Crome, I. B., et al. BAP updated guidelines: evidence based guidelines for the pharmacological management of substance abuse, harmful use, addiction and comorbidity: recommendations from BAP (2012) Journal of Psychopharmacology 1-54 http://jop.sagepub.com/content/26/7/899 Findings (2014) Authoritative review reveals limitations of medicatingdependence http://findings.org.uk/count/downloads/download.php?file=Lingford_Hughes_AR_2.txt. Luty. J., (2015) Drug and alcohol addiction: new pharmacotherapies. B J Prych Advances (21), 33-41 doi: 10.1192/apt.bp.114.013367 NICE (2007) Drug Misuse: naltrexone for the management of opioid dependence (NICE technology appraisal,TA115) http://www.nice.org.uk/guidance/TA115 NICE (2007) Drug misuse: methadone and buprenorphine maintenance (NICE technology appraisal, TA114) http://www.nice.org.uk/guidance/TA114 NICE (2007) Drug misuse: opioid detoxification (NICE clinical guideline, CG52) http://www.nice.org.uk/CG52 NICE (2007) Drug misuse: psychosocial interventions (NICE clinical guideline, CG51) http://www.nice.org.uk/CG51 NICE (2010) Alcohol-use disorders: physical complications (NICE clinical guideline, CG100) http://guidance.nice.org.uk/CG100 NICE (2011) Alcohol use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence (NICE clinical guideline, CG115) http://guidance.nice.org.uk/CG115 Royal College of Psychiatrists (2011) Our invisible addicts First Report of the Older Persons’ Substance Misuse Working Group of the Royal College of Psychiatrists. http://www.rcpsych.ac.uk/files/pdfversion/cr165.pdf