Post-acute-withdrawal syndrome

Last updated
Post-acute-withdrawal syndrome
Other namesPost-withdrawal syndrome, protracted withdrawal syndrome, prolonged withdrawal syndromes
Specialty Psychiatry, Toxicology

Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after withdrawal from alcohol, [1] [2] opiates, benzodiazepines, antidepressants, and other substances. [3] [4] [5] Infants born to mothers who used substances of dependence during pregnancy may also experience a PAWS. [6] [7] While PAWS has been frequently reported by those withdrawing from opiate and alcohol dependence, the research has limitations. Protracted benzodiazepine withdrawal has been observed to occur in some individuals prescribed benzodiazepines. [8] [9]

Contents

Drug use, including alcohol and prescription drugs, can induce symptomatology which resembles mental illness. This can occur both in the intoxicated state and during the withdrawal state. In some cases these substance-induced psychiatric disorders can persist long after detoxification from amphetamine, cocaine, opioid, and alcohol use, causing prolonged psychosis, anxiety or depression. A protracted withdrawal syndrome can occur with symptoms persisting for months to years after cessation of substance use. Benzodiazepines, opioids, alcohol, and any other drug may induce prolonged withdrawal and have similar effects, with symptoms sometimes persisting for years after cessation of use. Psychosis including severe anxiety and depression are commonly induced by sustained alcohol, opioid, benzodiazepine, and other drug use which in most cases abates with prolonged abstinence. Any continued use of drugs or alcohol may increase anxiety, psychosis, and depression levels in some individuals. In almost all cases drug-induced psychiatric disorders fade away with prolonged abstinence, although permanent damage to the brain and nervous system may be caused by continued substance use. [10]

Signs and symptoms

Symptoms can sometimes come and go with wave-like re-occurrences or fluctuations in severity of symptoms. Common symptoms include impaired cognition, irritability, depressed mood, and anxiety; all of which may reach severe levels which can lead to relapse. [11] [12]

The protracted withdrawal syndrome from benzodiazepines, opioids, alcohol and other addictive substances can produce symptoms identical to generalized anxiety disorder as well as panic disorder. Due to the sometimes prolonged nature and severity of benzodiazepine, opioid and alcohol withdrawal, abrupt cessation is not advised. [13]

Hypothesized symptoms of PAWS are: [14] [15] [16] [17]

Symptoms occur intermittently, but are not always present. They are made worse by stress or other triggers and may arise at unexpected times and for no apparent reason. They may last for a short while or longer. Any of the following may trigger a temporary return or worsening of the symptoms of PAWS:[ citation needed ]

Post-acute benzodiazepine withdrawal

Disturbances in mental function can persist for several months or years after withdrawal from benzodiazepines. Psychotic depression persisting for more than a year following benzodiazepine withdrawal has been documented in the medical literature. The patient had no prior psychiatric history. The symptoms reported in the patient included, major depressive disorder with psychotic features, including persistent depressed mood, poor concentration, decreased appetite, insomnia, anhedonia, anergia and psychomotor retardation. The patient also experienced paranoid ideation (believing she was being poisoned and persecuted by co-employees), accompanied by sensory hallucinations. Symptoms developed after abrupt withdrawal of chlordiazepoxide and persisted for 14 months. Various psychiatric medications were trialed which were unsuccessful in alleviating the symptomatology. Symptoms were completely relieved by recommending chlordiazepoxide for irritable bowel syndrome 14 months later. [19] Another case report noted a similar phenomenon in a female patient who abruptly reduced her diazepam dosage from 30 mg to 5 mg per day. She developed electric shock sensations, depersonalization, anxiety, dizziness, left temporal lobe EEG spiking activity, hallucinations, visual perceptual and sensory distortions which persisted for years. [20]

A clinical trial of patients taking the benzodiazepine alprazolam (Xanax) for eight weeks triggered protracted symptoms of memory deficits which were still present after up to eight weeks post cessation of alprazolam. [21]

Dopamine agonist protracted withdrawal

After long-term use of dopamine agonists, a withdrawal syndrome may occur during dose reduction or discontinuation with the following possible side effects: anxiety, panic attacks, dysphoria, depression, agitation, irritability, suicidal ideation, fatigue, orthostatic hypotension, nausea, vomiting, diaphoresis, generalized pain, and drug cravings. For some individuals, these withdrawal symptoms are short-lived and make a full recovery, for others a protracted withdrawal syndrome may occur with withdrawal symptoms persisting for months or years. [22]

Cause

The syndrome may be in part due to persisting physiological adaptations in the central nervous system manifested in the form of continuing but slowly reversible tolerance, disturbances in neurotransmitters and resultant hyperexcitability of neuronal pathways. [23] [24] [25] [26] However, data supports "neuronal and overwhelming cognitive normalization" in regards to chronic amphetamine use and PAWS. [27] [28] Stressful situations arise in early recovery, and the symptoms of post acute withdrawal syndrome produce further distress. It is important to avoid or to deal with the triggers that make post acute withdrawal syndrome worse. The types of symptomatology and impairments in severity, frequency, and duration associated with the condition vary depending on the drug of use.

Treatment

The condition gradually improves over a period of time which can range from six months to several years in more severe cases. [29] [30]

Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4 to 266 weeks. [31] This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.

Acamprosate has been found to be effective in alleviating some of the post acute withdrawal symptoms of alcohol withdrawal. [32] [33] Carbamazepine or trazodone may also be effective in the treatment of post acute withdrawal syndrome in regards to alcohol use. [34] [35] [36] Cognitive behavioral therapy can also help the post acute withdrawal syndrome especially when cravings are a prominent feature. [37]

See also

Related Research Articles

<span class="mw-page-title-main">Alcoholism</span> Problematic excessive alcohol consumption

Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records, the World Health Organization (WHO) estimated there were 283 million people with alcohol use disorders worldwide as of 2016. The term alcoholism was first coined in 1852, but alcoholism and alcoholic are stigmatizing and discourage seeking treatment, so clinical diagnostic terms such as alcohol use disorder or alcohol dependence are used instead.

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955 and was made available in 1960 by Hoffmann–La Roche, who soon followed with diazepam (Valium) in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Diazepam</span> Benzodiazepine sedative


Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. When taken by mouth, effects begin after 15 to 60 minutes.

<span class="mw-page-title-main">Alprazolam</span> Benzodiazepine medication

Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly used in management of anxiety disorders, specifically panic disorder or generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.

<span class="mw-page-title-main">Sedative</span> Drug that reduces excitement without inducing sleep

A sedative or tranquilliser is a substance that induces sedation by reducing irritability or excitement. They are CNS depressants and interact with brain activity causing its deceleration. Various kinds of sedatives can be distinguished, but the majority of them affect the neurotransmitter gamma-aminobutyric acid (GABA). In spite of the fact that each sedative acts in its own way, most produce relaxing effects by increasing GABA activity.

Drug withdrawal, drug withdrawal syndrome, or substance withdrawal syndrome, is the group of symptoms that occur upon the abrupt discontinuation or decrease in the intake of pharmaceutical or recreational drugs.

<span class="mw-page-title-main">Triazolam</span> Triazolobenzodiazepine class medication

Triazolam, sold under the brand name Halcion among others, is a central nervous system (CNS) depressant tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepine (BZD) derivatives. It possesses pharmacological properties similar to those of other benzodiazepines, but it is generally only used as a sedative to treat severe insomnia. In addition to the hypnotic properties, triazolam's amnesic, anxiolytic, sedative, anticonvulsant, and muscle relaxant properties are pronounced as well.

<span class="mw-page-title-main">Bromazepam</span> Benzodiazepine drug

Bromazepam, sold under many brand names, is a benzodiazepine. It is mainly an anti-anxiety agent with similar side effects to diazepam. In addition to being used to treat anxiety or panic states, bromazepam may be used as a premedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets.

<span class="mw-page-title-main">Oxazepam</span> Benzodiazepine medication

Oxazepam is a short-to-intermediate-acting benzodiazepine. Oxazepam is used for the treatment of anxiety and insomnia and in the control of symptoms of alcohol withdrawal syndrome.

Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certain medications such as benzodiazepines, opioids, stimulants, antiepileptics and antidepressants, as well as the recreational misuse of drugs such as alcohol, opioids and benzodiazepines. The higher the dose used, the greater the duration of use, and the earlier age use began are predictive of worsened physical dependence and thus more severe withdrawal syndromes. Acute withdrawal syndromes can last days, weeks or months. Protracted withdrawal syndrome, also known as post-acute-withdrawal syndrome or "PAWS", is a low-grade continuation of some of the symptoms of acute withdrawal, typically in a remitting-relapsing pattern, often resulting in relapse and prolonged disability of a degree to preclude the possibility of lawful employment. Protracted withdrawal syndrome can last for months, years, or depending on individual factors, indefinitely. Protracted withdrawal syndrome is noted to be most often caused by benzodiazepines. To dispel the popular misassociation with addiction, physical dependence to medications is sometimes compared to dependence on insulin by persons with diabetes.

Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individual's functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal and that necessitates the re-consumption of the drug. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. ΔFosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence.

<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.

<span class="mw-page-title-main">Loprazolam</span> Benzodiazepine

Loprazolam (triazulenone) marketed under many brand names is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It is licensed and marketed for the short-term treatment of moderately-severe insomnia.

<span class="mw-page-title-main">Benzodiazepine withdrawal syndrome</span> Signs and symptoms due to benzodiazepines discontinuation in physically dependent persons

Benzodiazepine withdrawal syndrome is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.

<span class="mw-page-title-main">Alcohol withdrawal syndrome</span> Medical condition

Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. More severe symptoms may include seizures, and delirium tremens (DTs); which can be fatal in untreated patients. Symptoms start at around 6 hours after last drink. Peak incidence of seizures occurs at 24-36 hours and peak incidence of delirium tremens is at 48-72 hours.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

<span class="mw-page-title-main">Effects of long-term benzodiazepine use</span>

The effects of long-term benzodiazepine use include drug dependence as well as the possibility of adverse effects on cognitive function, physical health, and mental health. Long-term use is sometimes described as use not shorter than three months. Benzodiazepines are generally effective when used therapeutically in the short term, but even then the risk of dependency can be significantly high. There are significant physical, mental and social risks associated with the long-term use of benzodiazepines. Although anxiety can temporarily increase as a withdrawal symptom, there is evidence that a reduction or withdrawal from benzodiazepines can lead in the long run to a reduction of anxiety symptoms. Due to these increasing physical and mental symptoms from long-term use of benzodiazepines, slow withdrawal is recommended for long-term users. Not everyone, however, experiences problems with long-term use.

<span class="mw-page-title-main">Panic disorder</span> Anxiety disorder characterized by reoccurring unexpected panic attacks

Panic disorder is a mental and behavioral disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear that may include palpitations, sweating, shaking, shortness of breath, numbness, or a feeling that something terrible is going to happen. The maximum degree of symptoms occurs within minutes. There may be ongoing worries about having further attacks and avoidance of places where attacks have occurred in the past.

Kindling due to substance withdrawal is the neurological condition which results from repeated withdrawal episodes from sedative–hypnotic drugs such as alcohol and benzodiazepines.

<span class="mw-page-title-main">Prescription drug addiction</span> Medical condition

Prescription drug addiction is the chronic, repeated use of a prescription drug in ways other than prescribed for, including using someone else’s prescription. A prescription drug is a pharmaceutical drug that may not be dispensed without a legal medical prescription. Drugs in this category are supervised due to their potential for misuse and substance use disorder. The classes of medications most commonly abused are opioids, central nervous system (CNS) depressants and central nervous stimulants. In particular, prescription opioid is most commonly abused in the form of prescription analgesics.

References

  1. ↑ Stephen Rich J, Martin PR (2014). "Co-occurring psychiatric disorders and alcoholism". Alcohol and the Nervous System. Handbook of Clinical Neurology. Vol. 125. pp. 573–88. doi:10.1016/B978-0-444-62619-6.00033-1. ISBN   9780444626196. PMID   25307597.{{cite book}}: |journal= ignored (help)
  2. ↑ Koob, George F. (2009). "Dynamics of Neuronal Circuits in Addiction: Reward, Antireward, and Emotional Memory". Pharmacopsychiatry. 42 (Suppl 1): S32–S41. doi:10.1055/s-0029-1216356. ISSN   0176-3679. PMC   2739305 . PMID   19434554.
  3. ↑ Collier, Judith; Longmore, Murray (2003). "4". In Scally, Peter (ed.). Oxford Handbook of Clinical Specialties (6 ed.). Oxford University Press. p. 366. ISBN   978-0-19-852518-9.
  4. ↑ Ashton H (1991). "Protracted withdrawal syndromes from benzodiazepines". J Subst Abuse Treat. 8 (1–2). benzo.org.uk: 19–28. doi:10.1016/0740-5472(91)90023-4. PMID   1675688.
  5. ↑ Wu JM; Wei DY; Luo YF; Xiang XY (November 2003). "[Clinic research on heroin de-addiction effects of acupuncture and its potentiality of preventing relapse]". Zhong Xi Yi Jie He Xue Bao. 1 (4): 268–72. doi:10.3736/jcim20030412. PMID   15339529.
  6. ↑ Lejeune C; Floch-Tudal C; Montamat S; Crenn-Hebert C; Simonpoli AM (March 1997). "[Management of drug addict pregnant women and their children]". Arch Pediatr. 4 (3): 263–70. doi:10.1016/S0929-693X(97)87247-8. PMID   9181022.
  7. ↑ Gaillard MC; Borruat FX (April 2002). "[New finding: transitory horizontal pendular nystagmus secondary to neonatal abstinence syndrome]". Klin Monatsbl Augenheilkd. 219 (4): 317–9. doi:10.1055/s-2002-30650. PMID   12022028. S2CID   72584335.
  8. ↑ Satel SL (May 1993). "Should protracted withdrawal from drugs be included in DSM-IV?". American Journal of Psychiatry. 150 (5): 695–704. doi:10.1176/ajp.150.5.695. PMID   8097618.
  9. ↑ Ashton H (1991). "Protracted withdrawal syndromes from benzodiazepines". J Subst Abuse Treat. 8 (1–2): 19–28. doi:10.1016/0740-5472(91)90023-4. PMID   1675688.
  10. ↑ Evans, Katie; Sullivan, Michael J. (1 March 2001). Dual Diagnosis: Counseling the Mentally Ill Substance Abuser (2nd ed.). Guilford Press. pp. 75–76. ISBN   978-1-57230-446-8.
  11. ↑ Stojek A; Madejski J; Dedelis E; Janicki K (May–Jun 1990). "[Correction of the symptoms of late substance withdrawal syndrome by intra-conjunctival administration of 5% homatropine solution (preliminary report)]". Psychiatr Pol. 24 (3): 195–201. PMID   2084727.
  12. ↑ Bokhan NA; Abolonin AF; Krylov EN; Vetlugina TP; Ivanova SA (2003). "Comparative Efficiency of Proproten-100 during the Therapy of Patients with Alcoholism in the Stage of Therapeutic Remission". Bull Exp Biol Med. 135 (Suppl 1): 171–5. doi:10.1023/A:1024709014483. PMID   12949690. S2CID   10798202.
  13. 1 2 3 Riba, Michelle B.; Ravindranath, Divy (12 April 2010). Clinical manual of emergency psychiatry. Washington, DC: American Psychiatric Publishing Inc. p. 197. ISBN   978-1-58562-295-5.
  14. ↑ De Soto CB; O'Donnell WE; Allred LJ; Lopes CE (December 1985). "Symptomatology in alcoholics at various stages of abstinence". Alcohol Clin Exp Res . 9 (6): 505–12. doi:10.1111/j.1530-0277.1985.tb05592.x. PMID   3911810.
  15. ↑ Voltaire-Carlsson A; Hiltunen AJ; Koechling UM; Borg S (Sep–Oct 1996). "Effects of long-term abstinence on psychological functioning: a prospective longitudinal analysis comparing alcohol-dependent patients and healthy volunteers". Alcohol. 13 (5): 415–21. doi:10.1016/0741-8329(96)81678-8. PMID   8888936.
  16. ↑ Watanabe KI; Ogihara-Hashizume A; Kobayashi Y; Mitsushio H; Komiyama T (April 2001). "Impaired sleep during the post-alcohol withdrawal period in alcoholic patients". Addict Biol. 6 (2): 163–169. doi:10.1080/13556210020040244. PMID   11341856. S2CID   38350347.
  17. ↑ Vik PW; Cellucci T; Jarchow A; Hedt J (March 2004). "Cognitive impairment in substance abuse". Psychiatr Clin North Am. 27 (1): 97–109. doi:10.1016/S0193-953X(03)00110-2. PMID   15062633.
  18. ↑ Janiri L; Martinotti G; Dario T; Reina D; Paparello F; Pozzi G; Addolorato G; Di Giannantonio M; De Risio S (June 3, 2005). "Anhedonia and substance-related symptoms in detoxified substance-dependent subjects: a correlation study". Neuropsychobiology. 52 (1): 37–44. doi:10.1159/000086176. PMID   15942262. S2CID   22464794.
  19. ↑ Modell JG (Mar–Apr 1997). "Protracted benzodiazepine withdrawal syndrome mimicking psychotic depression" (PDF). Psychosomatics. 38 (2). Psychiatry Online: 160–1. doi:10.1016/S0033-3182(97)71493-2. PMID   9063050. Archived from the original (PDF) on 2008-06-25. Retrieved 2010-05-31.
  20. ↑ Shader RI; Greenblatt DJ (1981). "The use of benzodiazepines in clinical practice". Br J Clin Pharmacol. 11 (Suppl 1): 5S–9S. doi:10.1111/j.1365-2125.1981.tb01832.x. PMC   1401641 . PMID   6133535.
  21. ↑ Curran, Hv; Bond, A; O'Sullivan, G; Bruce, M; Marks, I; Lelliot, P; Shine, P; Lader, M (November 1994). "Memory functions, alprazolam and exposure therapy: a controlled longitudinal study of agoraphobia with panic disorder". Psychological Medicine. 24 (4): 969–76. doi:10.1017/S0033291700029056. ISSN   0033-2917. PMID   7892364. S2CID   38165723.
  22. ↑ Nirenberg MJ (2013). "Dopamine agonist withdrawal syndrome: implications for patient care". Drugs Aging. 30 (8): 587–92. doi:10.1007/s40266-013-0090-z. PMID   23686524. S2CID   207489653.
  23. ↑ Rimondini R; Sommer WH; Dall'Olio R; Heilig M (March 2008). "Long-lasting tolerance following a history of dependence". Addict Biol. 13 (1): 26–30. doi:10.1111/j.1369-1600.2007.00079.x. PMID   17850416. S2CID   22263141.
  24. ↑ Ahveninen J; Jääskeläinen IP; Pekkonen E; Hallberg A; Hietanen M; Näätänen R; Sillanaukee P (June 8, 1999). "Post-withdrawal changes in middle-latency auditory evoked potentials in abstinent human alcoholics". Neurosci Lett. 268 (2): 57–60. doi:10.1016/S0304-3940(99)00378-X. PMID   10400077. S2CID   8525967.
  25. ↑ Kiefer F; Andersohn F; Jahn H; Wolf K; Raedler TJ; Wiedemann K (January 2002). "Involvement of plasma atrial natriuretic peptide in protracted alcohol withdrawal". Acta Psychiatr Scand . 105 (1): 65–70. doi:10.1034/j.1600-0447.2002.0_011.x. PMID   12086228. S2CID   29059697.
  26. ↑ Bruijnzeel AW; Gold MS (November 2005). "The role of corticotropin-releasing factor-like peptides in cannabis, nicotine, and alcohol dependence". Brain Res Brain Res Rev. 49 (3): 505–28. doi:10.1016/j.brainresrev.2005.01.007. PMID   16269317. S2CID   27909100.
  27. ↑ Hart, CL; Marvin, CB; Silver, R; Smith, EE (Feb 2012). "Is cognitive functioning impaired in methamphetamine users? A critical review". Neuropsychopharmacology. 37 (3): 586–608. doi:10.1038/npp.2011.276. PMC   3260986 . PMID   22089317.
  28. ↑ Salo, Ruth; Buonocore, Michael; Laemon, Martin (2011-01-15). "Extended findings of brain metabolite normalization in MA-dependent subjects across sustained abstinence: A proton MRS study". Drug and Alcohol Dependence. 113 (2–3): 133–138. doi:10.1016/j.drugalcdep.2010.07.015. PMC   3000435 . PMID   20739127.
  29. ↑ Roberts AJ; Heyser CJ; Cole M; Griffin P; Koob GF (June 2000). "Excessive ethanol drinking following a history of dependence: animal model of allostasis". Neuropsychopharmacology. 22 (6): 581–94. doi:10.1016/S0893-133X(99)00167-0. PMID   10788758. S2CID   24384085.
  30. ↑ De Soto CB, O'Donnell WE, De Soto JL (October 1989). "Long-term recovery in alcoholics". Alcohol Clin Exp Res. 13 (5): 693–7. doi:10.1111/j.1530-0277.1989.tb00406.x. PMID   2688470.
  31. ↑ L. Saxon; S. Borg & A. J. Hiltunen (August 2010). "Reduction of aggression during benzodiazepine withdrawal: effects of flumazenil". Pharmacology Biochemistry and Behavior . 96 (2): 148–151. doi:10.1016/j.pbb.2010.04.023. PMID   20451546. S2CID   41351863.
  32. ↑ Beleslin D (1991). "[Modern drug therapy in alcoholism]". Med Pregl. 44 (7–8): 279–84. PMID   1806768.
  33. ↑ Wilde MI; Wagstaff AJ (June 1997). "Acamprosate. A review of its pharmacology and clinical potential in the management of alcohol dependence after detoxification". Drugs. 53 (6): 1038–53. doi:10.2165/00003495-199753060-00008. PMID   9179530. S2CID   195691152.
  34. ↑ Malcolm R; Myrick H; Brady KT; Ballenger JC (2001). "Update on anticonvulsants for the treatment of alcohol withdrawal". Am J Addict. 10 Suppl (1): 16–23. doi:10.1080/10550490150504100. PMID   11268817.
  35. ↑ Le Bon O; Murphy JR; Staner L; Hoffmann G; Kormoss N; Kentos M; Dupont P; Lion K; Pelc I; Verbanck P (August 2003). "Double-blind, placebo-controlled study of the efficacy of trazodone in alcohol post-withdrawal syndrome: polysomnographic and clinical evaluations". J Clin Psychopharmacol. 23 (4): 377–83. doi:10.1097/01.jcp.0000085411.08426.d3. PMID   12920414. S2CID   33686593.
  36. ↑ Mueller TI; Stout RL; Rudden S; Brown RA; Gordon A; Solomon DA; Recupero PR (February 1997). "A double-blind, placebo-controlled pilot study of carbamazepine for the treatment of alcohol dependence". Alcohol Clin Exp Res. 21 (1): 86–92. doi:10.1111/j.1530-0277.1997.tb03733.x. PMID   9046378.
  37. ↑ Hori T; Komiyama T; Harada S; Matsumoto T (2005). "[Treatment of substance dependence by a bio-cognitive model based on behavioral pharmacology]". Seishin Shinkeigaku Zasshi. 107 (11): 1147–58. PMID   16408423.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.