Substance Use Disorder Pharmacotherapy
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Direct answer
Because withdrawal and craving, not weak will, drive relapse in opioid use disorder, medication is first-line treatment: buprenorphine, a partial mu agonist with a ceiling on respiratory depression, and methadone, a full agonist with a long variable half-life, both hold withdrawal at bay without euphoria; naltrexone blocks opioids but only after seven to ten detoxified days. Tobacco dependence has three evidence-based options — nicotine replacement, varenicline and bupropion. Cannabis and stimulant use disorders still lack approved pharmacotherapy and rest on psychosocial intervention. Naloxone reverses overdose, and its short half-life of 30 to 90 minutes makes take-home naloxone and repeat dosing core harm reduction.
What you must remember
- Buprenorphine properties: sublingual partial agonist, high receptor affinity (it displaces full agonists — hence precipitated withdrawal if started too early), ceiling on respiratory depression; combined with naloxone to deter injection.
- Induction timing: wait for mild-to-moderate withdrawal (COWS around 8 or more) before the first buprenorphine dose; starting early trades craving for precipitated misery.
- Methadone: once-daily full agonist, half-life 24-36 hours and variable — accumulation risk, QT prolongation, and only licensed centres dispense it in India.
- Naltrexone rules: only after 7-10 days opioid-free; on relapse the blocked tolerance has vanished, making overdose the lethal risk; monthly injection exists for adherence.
- Naloxone rescue: 0.4-0.8 mg IV or intranasal, short-acting — expect re-narcotisation and repeat dosing; prescribe it to patients and families.
- Varenicline: partial alpha-4 beta-2 nicotinic agonist — start one week before the quit date, titrate to 1 mg twice daily; nausea and vivid dreams; most effective single agent.
- Bupropion: NDRI, contraindicated with seizures, eating disorders and MAOIs; halves craving and limits weight gain after quitting.
- Vacuum areas: no approved drugs for cannabis, cocaine or methamphetamine dependence — contingency management and behavioural therapy carry those.
Starting buprenorphine without precipitating withdrawal
The first buprenorphine dose is the whole examination. A man using heroin by injection presents in early withdrawal — yawning, lacrimation, pilomotor erection, COWS 6. Dosing now would flood high-affinity receptors with a partial agonist and hurl him into full withdrawal; wait until the score passes 8-12, then give 2-4 mg sublingually and observe. Titrate over two days to a dose that abolishes craving without sedation. The naloxone component stays sublingually inactive but punishes injection. If he later chooses abstinence, naltrexone follows only after a naloxone challenge or ten clean days.
Tobacco runs in parallel: combination nicotine replacement (patch plus gum for breakthrough craving) doubles quit rates over placebo; varenicline outperforms both single-mode therapies and suits the smoker with past depression concerns; bupropion serves the one who cannot stop while also on an antidepressant. Every quit attempt deserves at least 12 weeks of pharmacotherapy.
Indian programme context
India delivers opioid substitution therapy through NACO-supported targeted-intervention centres under the National AIDS Control Programme, dispensing free buprenorphine-naloxone to injecting drug users — a harm-reduction pathway an MBBS graduate should be able to describe. Methadone is confined to designated government centres. De-addiction services cluster around "Nasha Mukti" centres and hospital psychiatry departments; the NDPS Act schedules most agents involved. Over-the-counter codeine and tramadol misuse supplies a steady stream of iatrogenic dependence — prescribe, count and report misuse patterns to the PvPI.
Frequently asked questions
Why is buprenorphine combined with naloxone?
Naloxone is inactive sublingually but, if the tablet is dissolved and injected, it precipitates withdrawal — pure deterrence while oral-sublingual therapy proceeds normally.
What is precipitated withdrawal and how is it avoided?
High-affinity buprenorphine displaces full agonists from receptors; waiting until mild-to-moderate withdrawal (COWS 8 or more) before induction prevents it.
Why prescribe take-home naloxone?
Its half-life of 30-90 minutes is shorter than most opioids, so reversed patients re-sedate; families equipped and trained with intranasal naloxone bridge the gap to hospital.
What is varenicline's mechanism and main adverse effects?
Partial agonism at alpha-4 beta-2 nicotinic receptors eases craving while blocking reinforcement; nausea, vivid dreams and insomnia head the adverse profile.
Which substance use disorders have no approved pharmacotherapy?
Cannabis and stimulant (cocaine, amphetamine-type) dependence — psychosocial and contingency-based interventions remain the standard of care.