Neuroadaptation, Tolerance, and Withdrawal Neuroadaptation is the brains response to over stimulation from drugs. Sedation and stimulation (intoxication) are the result of excessive drug-specific effects on brain functions. Tolerance is the process by which the reward and pleasure centers of the brain adapt to high concentrations of pleasure neurotransmitters. In direct response to overstimulation, the brain regions decrease in sensitivity and become unresponsive (deaf) to normal levels of stimulation. In addition to pleasure circuits each drug type affects other brain functions.. Other brain pathways overstimulated by drugs also neuroadapt and become under active, directly leading to anxiety, depression, and loss of energy. Once neuroadaptation develops (tolerance), there will always be Withdrawal symptoms that are the mirror image of the drug effects. Cessation of drug use leads to inversion of the high; sobriety becomes pleasureless, anxious, sleepless, and lacking energy Under unstimulated conditions (without drugs) there is profound interference with the ability to experience normal pleasure. When sober, the user experiences Craving : anhedonia, anxiety, anger, frustration. The pleasure system remains impaired for months to years, interfering with sobriety, learning, and impulse inhibition.
Compulsion: loss of control The user cant not do it s/he is compelled to use. Compulsion is not rational and is not planned. Continued use despite adverse consequences An addict is a person who uses even though s/he knows it is causing problems. Addiction is staged based on adverse consequences. Craving: daily symptom of the disease The user experiences intense psychological preoccupation with getting and using the drug. Craving is dysphoric, agitating and it feels very bad. Denial/hypofrontality: distortion of cognition caused by craving Under the pressure of intense craving, the user is temporarily blinded to the risks and consequences of using. Definition of Addiction
Causes of Craving in Addicts EWMS Environmental cues (Triggers ) immediate, catastrophic, overwhelming craving stimulated by people, places, things associated with prior drug-use experiences Drug Withdrawal inadequately treated or untreated Mental illness symptoms inadequately treated or untreated Stress equals craving
Physical Dependence Tolerance Neuroadaptation forces the user to increase the dose to maintain the effect of the drug. Using an inadequate dose causes withdrawal: symptoms occur when the amount used is less than the tolerance level. Physical Dependence When the user stops the drug, physical illness results. Abstinence Syndrome Name of the illness caused by withdrawal symptoms.
Core Principles in the Use of Opiates for Treatment of Chronic Pain: 1.Detox from all sedative-hypnotic drugs, with meticulous attention to avoid all withdrawal symptoms 2.Substitute all opiates with sustained-release or long-acting opiates: MS Contin, methadone, suboxone 3.Titrate dose to optimum, the dose that relieves pain and relieves pain without sedation 4.Avoid use of "breakthrough" medication
Overview of Buprenorphine (Suboxone and Subutex) Highly safe medication (acute & chronic dosing). Primary side effects: like other mu agonist opioids (e.g.,nausea, constipation) but may be less severe. No evidence of significant disruption in cognitive or psychomotor performance with buprenorphine maintenance. No evidence of organ damage with chronic dosing. Use of Buprenorphine in the Pharmacologic Management of Opioid Dependence: A Curriculum of Physicians. (eds: Strain EC, Trhumble JG, Jara GB) CSAT. 2001
Kakko J, et.al. 1-year retention and social function after buprenorphine-assisted relapse prevention treatment for heroin dependence in Sweden_ a randomised, placebo-controlled trial The Lancet 361 (9358) et.al One Year Outcome of Opiate Treatment Overall, the dismal outcome for our controls reiterates the grave nature of heroin dependence, and shows the considerable health and social difficulties faced by our patients. Furthermore, the severity of problems in our patient sample is tragically emphasised by the 20% mortality in the controls over the course of a 1-year study.
Opiate Progression Pills to the Needle Historically, untreated dependence on prescription opiates led to a trajectory from Pills ingested orally Pills crushed and snorted or smoked Pills injected Heroin snorted or smoked Heroin used intravenously This progression develops over from 12 to 24 months
A 33-year follow-up of narcotics addicts.
Special Problems in Former Opiate Addicts Persons previously addicted to opiates Have low pain tolerance because endogenous analgesic mechanisms are impaired. Will uncover their previous level of opiate tolerance over weeks and require upward dosage titration over an extended time (despite years of abstinence). Require doses 2 to 4 times higher for analgesia than non-tolerant persons (due to high opiate tolerance). Need slower, symptom-driven tapers to discontinue opiates.
C I M Model Treatment Withdrawal Management PRINCIPLES Calculate the dose equivalent per 24 hours Push medications to achieve symptom capture Maintain Diastolic BP <90 and Pulse <90 Decrease substitute medication in 10% increments Slow rate of taper to maintain Diastolic BP <90 and Pulse <90 Tremor free SUBSTITUTION TAPER
Withdrawal Management Opiate Substitution Query: time since last opiate use Query: all opiates used in past 7 days. Calculate client's usual 24 hour opiate dose. Query: prior withdrawal experience(s). Query: other drugs used: alcohol illicit drugs prescription medications over-the-counter preparations Determine if client requires other detoxification
Withdrawal Management Substitution Methodology Opiates Calculate Suboxone dose using opiate dose equivalents. Give first Suboxone dose (2 - 8 mg) when objective and clear signs of withdrawal are evident. Record Pulse, BP, and withdrawal SX on Symptom Assessment sheet. Recheck Pulse & Blood Pressure after 90 minutes. Give 1/4 of estimated daily Suboxone dose when withdrawal symptoms reappear. Give the remainder of Suboxone in divided doses every hours.
Withdrawal Management Completion of Substitution Phase Substitution is complete when the patient feels normal, and craving goes away. Persistence of insomnia, anxiety, pain, or depression indicate need for separate treatment of these symptoms (dual diagnosis). The patient is now ready for taper or for maintenance.
Withdrawal Management Taper Phase There are two variables in tapering: Dose: how much to taper Time: how often to taper Dose reductions are adjusted so that the patient does not re-enter withdrawal. If withdrawal symptoms develop during taper, return to previous effective dose, reduce amount of taper (dose) or lengthen the (time) interval. Do not continue until symptoms subside. Monitor Pulse and Blood Pressure daily Complete Symptom Assessment sheet daily. Adjust amount decreased and time between decreases to maintain symptom scores at 0-1
C I M Model Treatment Components of Treatment Initiation of Abstinence: Stopping Use Drug Detoxification: Use of medications to control withdrawal symptoms Avoidance Strategies: Measures to protect the client from environmental cues Schedule: Establishing times for arising, mealtimes, and going to bed Mental Health Assessment and Treatment Relapse Prevention Drug Detoxification: Continued use of medications to control withdrawal Avoidance Strategies: Controlled re-entry to cue-rich environments Schedule: Adherence to a regular daily lifestyle - HUNGRYThree regularly spaced meals each day - ANGRYSeparate feelings of anger from losing control of behavior - LONELY One positive social contact per day minimum - TIREDDaily practice of sleep hygiene Tools: Behaviors that dissipate craving Exercise Spiritual Practice Talk Peer Support Groups Counseling Having Fun Mental Health Treatment
C I M Model Treatment Relapse Prevention Workshop Principles Addicted persons relapse because of craving. Craving has causes that can be predicted, recognized and analyzed. Craving can be managed with the use of program activities. Questions about Craving What is your craving score? What is the cause of your craving? Environmental cue Stress Drug withdrawal Mental health problems What will you do to take care of yourself? Avoidance strategies Stress Management Tools Program activities
REFERENCES Benowitz N. Neurobiology of nicotine addiction: implications for smoking cessation treatment. American Journal of Medicine. 121(4A) S3-S10 (2008). Bechara A. Decision making, impulse control and loss of willpower to resit drugs: a neurocognitive perspective. Nature Neuroscience. 8: (2005) Dackis C, OBrien C. Neurobiology of addiction: treatment and public policy ramifications. Nature Neuroscience. 8(11): (2005). Nestler EJ, Malenka RC. The addicted brain. Scientific American.com February 9, Stalcup SA, Christian D, Stalcup JA, Brown M Galloway GP. A treatment model for craving identification and management. Journal of Psychoactive Drugs. 38:235-44, 2006 Volkow ND, Fowler JS, Wang GJ. The addicted human brain: insights from imaging studies. Journal of Clinical Investigation. 111(10: (2003). Weinberger DR, Elvevag B, Giedd JN. The adolescent brain: a work in progress. National Campaign to Prevent Teen Pregnancy. June 2005.