Post-acute-withdrawal syndrome

Short description: Hypothesized pattern of symptoms occurring months after drug cessation

Post-acute-withdrawal syndrome

Other names| Post-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 post-acute withdrawal syndrome.[6][7] While post-acute withdrawal syndrome 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]

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]

## Contents

* 1 Signs and symptoms
* 1.1 Post-acute benzodiazepine withdrawal
* 1.2 Dopamine agonist protracted withdrawal
* 2 Cause
* 3 Treatment
* 4 See also
* 5 References

## 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 post-acute withdrawal syndrome are:[14][15][16][17]

* Psychosocial dysfunction
* Anhedonia[18]
* Depression
* Impaired interpersonal skills
* Obsessive-compulsive behaviour
* Feelings of guilt
* Autonomic disturbances
* Pessimistic thoughts
* Impaired attentional control
* Lack of initiative
* Craving
* Inability to think clearly
* Memory problems
* Emotional overreactions or numbness
* Sleep disturbances
* Extreme fatigue
* Physical coordination problems
* Stress sensitivity
* Increased sensitivity to pain
* Panic disorder[13]
* Psychosis
* Generalized anxiety disorder[13]
* Sleep disturbance (dreams of using, behaviors associated with the life style)
* Mourning (the change in lifestyle)

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 post-acute withdrawal syndrome:[citation needed]

* Stressful and/or frustrating situations
* Multitasking
* Feelings of anxiety, fearfulness or anger
* Social conflicts
* Unrealistic expectations of oneself

### 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, reported 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, depersonalisation, 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

* Alcohol withdrawal syndrome
* Antidepressant discontinuation syndrome
* Benzodiazepine withdrawal syndrome
* Opioid use disorder

## References

1. ↑ "Co-occurring psychiatric disorders and alcoholism". Alcohol and the Nervous System. Handbook of Clinical Neurology. 125. 2014. 573–88. doi:10.1016/B978-0-444-62619-6.00033-1. ISBN 9780444626196.
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. PMID 19434554.
3. ↑ Collier, Judith; Longmore, Murray (2003). "4". in Scally, Peter. 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 (benzo.org.uk) 8 (1–2): 19–28. doi:10.1016/0740-5472(91)90023-4. PMID 1675688. http://www.benzo.org.uk/ashpws.htm.
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.
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. https://pubmed.ncbi.nlm.nih.gov/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. https://books.google.com/books?id=lvUzR0obihEC.
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.
13. ↑ 13.0 13.1 13.2 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. https://books.google.com/books?id=l8veL1bDoF8C&pg=PA197.
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.
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 et al. (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.
19. ↑ Modell JG (Mar–Apr 1997). "Protracted benzodiazepine withdrawal syndrome mimicking psychotic depression". Psychosomatics (Psychiatry Online) 38 (2): 160–1. doi:10.1016/S0033-3182(97)71493-2. PMID 9063050. http://psy.psychiatryonline.org/cgi/reprint/38/2/160.pdf. 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. 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.
22. ↑ "Dopamine agonist withdrawal syndrome: implications for patient care". Drugs Aging 30 (8): 587–92. 2013. doi:10.1007/s40266-013-0090-z. PMID 23686524.
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.
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.
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.
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.
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. 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. 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.
30. ↑ "Long-term recovery in alcoholics". Alcohol Clin Exp Res 13 (5): 693–7. October 1989. 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.
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.
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 et al. (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.
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.

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