Alcohol Use Disorder: Dependence & Discontinuation
Alcohol Use Disorder, dependence and recovery. Neurobiology, withdrawal syndrome and modern treatment with pharmacogenomics by psychiatrist Paschalis Gkikas in Athens.
Alcohol Use Disorder: Dependence & Discontinuation
Alcohol is the legal, socially accepted substance with the greatest global disease burden among addictive substances. Alcohol Use Disorder is not a “lack of willpower” — it is a chronic neurobiological condition with proven effective treatments.
What is Alcohol Use Disorder?
Alcohol Use Disorder (AUD, ICD-10: F10) includes a spectrum of clinical presentations, from harmful use to full dependence, characterized by:
- Inability to control the amount or frequency of drinking
- Tolerance — the need for increasing amounts to achieve the same effect
- Withdrawal syndrome when alcohol is stopped
- Continued use despite serious negative consequences
- Neglect of social, occupational or recreational activities because of alcohol
- Significant time spent obtaining, drinking or recovering from alcohol
AUD affects approximately 5% of the global population — with significant underreporting because of social stigma.
Clinical presentation and symptoms
Acute alcohol use
- Reduced inhibitions, euphoria
- Dysarthria, ataxia, balance difficulty
- Slowed reflexes and reaction time
- Alcohol-related amnesia (“blackout”) at high alcohol levels
Chronic use
- Liver disease, such as fatty liver, hepatitis and cirrhosis
- Peripheral neuropathy
- Cardiomyopathy, arrhythmias
- Gastrointestinal complications, such as pancreatitis and gastritis
- Cognitive decline, Wernicke-Korsakoff syndrome due to vitamin B1 deficiency
- Depression, anxiety and insomnia as comorbidities or consequences of chronic use
Alcohol withdrawal syndrome
Alcohol withdrawal is one of the few substance-withdrawal syndromes that can be potentially fatal. It appears 6–24 hours after discontinuation and may include:
- Tremor, sweating, tachycardia, hypertension
- Anxiety, insomnia, nausea
- Seizures, usually 24–48 hours after discontinuation
- Delirium tremens, usually 48–72 hours after discontinuation — confusion, hallucinations and autonomic instability
Neurobiological basis
- GABA / glutamate imbalance: Alcohol enhances GABAergic inhibition and inhibits NMDA receptors. With chronic use, the brain compensates by reducing GABA receptors and increasing NMDA activity. This neuroadaptation is the basis of withdrawal syndrome after discontinuation.
- Dopaminergic reward system: Alcohol increases dopamine release in the nucleus accumbens — the same mechanism involved in other addictive substances. With chronic exposure, response to natural rewards decreases dramatically.
- Opioid system: Alcohol-induced endorphin release explains part of the euphoria — and is the therapeutic target of naltrexone.
- Epigenetic changes: Chronic use induces persistent changes in gene expression within reward pathways, contributing to the chronicity of the disorder.
- Prefrontal cortex: Progressive hypofunction, with reduced decision-making capacity, impulse control and evaluation of consequences.
Treatment approach
Phase 1: Medically supervised detoxification
Alcohol discontinuation in a dependent person should never be attempted without medical supervision. Paschalis Gkikas assesses the severity of dependence and designs a safe detoxification protocol:
- Benzodiazepines: Gold standard for preventing seizures and delirium tremens during withdrawal
- Vitamins: Intravenous thiamine (B1) to prevent Wernicke syndrome
- Electrolyte monitoring: Hypomagnesemia and hypokalemia are common complications
Phase 2: Maintenance of sobriety based on PGx
- Naltrexone: An opioid antagonist that reduces alcohol-induced euphoria and craving. Patients with the OPRM1 A118G variant show approximately double the effectiveness.
- Acamprosate: Regulates the GABA/glutamate balance, reducing discomfort and craving in early sobriety. It is particularly suitable for patients with intense withdrawal-related anxiety.
- Disulfiram: Inhibits aldehyde dehydrogenase — alcohol consumption while taking disulfiram causes a strong unpleasant reaction. Suitable for selected highly motivated patients.
- Treatment of comorbidity: Depression and anxiety disorders coexist in 50–60% of cases — pharmacological treatment, guided by PGx, is an integral part of addiction treatment.
Phase 3: Psychosocial interventions
- CBT for addiction: Identification of triggers, development of coping skills and relapse prevention
- Motivational Interviewing: Strengthening internal motivation for change
- Self-help groups: AA as a complementary component of treatment
Alcohol dependence is a chronic relapsing disease — not a failure. In Paschalis Gkikas’ practice, every relapse is analyzed as clinical information and as an opportunity to adjust the treatment plan, not as a reason to abandon treatment.
Frequently asked questions (FAQ)
What amount of alcohol is considered “dangerous”?
The WHO does not define a “safe” level of alcohol consumption. A “low-risk” level for adults is commonly defined as up to 14 units per week for men and 7 units per week for women, with at least two alcohol-free days. Any pattern of use that causes concern deserves assessment.
Can I stop suddenly if I drink heavily?
Sudden discontinuation in people with dependence is dangerous and potentially life-threatening because of withdrawal syndrome. Discontinuation should always be medically supervised.
Is the depression I feel caused by alcohol or independent?
Both are possible. Alcohol is a central nervous system depressant and can cause or worsen depression chronically. After adequate sobriety, usually 4–8 weeks, it is assessed whether depression persists independently — a distinction with important treatment implications.
Can rTMS help with alcohol dependence?
Emerging research data suggest that neuromodulation with rTMS over the prefrontal cortex may reduce craving and improve self-control. Paschalis Gkikas assesses suitability individually in selected cases.
