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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]

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]

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]}

• 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 PAWS:^{[citation needed]}

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

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]

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]

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.

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]

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