Post-acute withdrawal syndrome (PAWS) is a hypothesized set of persistent impairments that occur after

withdrawal Withdrawal means "an act of taking out" and may refer to: * Anchoresis (withdrawal from the world for religious or ethical reasons) * ''Coitus interruptus'' (the withdrawal method) * Drug withdrawal * Social withdrawal * Taking of money from a ban ...

from

alcohol Alcohol most commonly refers to: * Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom * Alcohol (drug), an intoxicant found in alcoholic drinks Alcohol may also refer to: Chemicals * Ethanol, one of sev ...

opiate An opiate, in classical pharmacology, is a substance derived from opium. In more modern usage, the term ''opioid'' is used to designate all substances, both natural and synthetic, that bind to opioid receptors in the brain (including antagonis ...

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes 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, ...

antidepressant Antidepressants are a class of medication used to treat major depressive disorder, anxiety disorders, chronic pain conditions, and to help manage addictions. Common side-effects of antidepressants include dry mouth, weight gain, dizziness, hea ...

s, and other substances. Infants born to mothers who used substances of dependence during pregnancy may also experience a post-acute withdrawal syndrome. While post-acute withdrawal syndrome has been reported by those in the recovery community, there have been few scientific studies supporting its existence outside of protracted benzodiazepine withdrawal. Because of this, the disorder is not recognized by the ''

Diagnostic and Statistical Manual of Mental Disorders The ''Diagnostic and Statistical Manual of Mental Disorders'' (DSM; latest edition: DSM-5-TR, published in March 2022) is a publication by the American Psychiatric Association (APA) for the classification of mental disorders using a common langua ...

'' or major medical associations. 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

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.

Benzodiazepine Benzodiazepines (BZD, BDZ, BZs), sometimes 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, ...

s, 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.

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. The protracted withdrawal syndrome from

opioid Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...

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. Hypothesized symptoms of post-acute withdrawal syndrome are: *

Psychosocial The psychosocial approach looks at individuals in the context of the combined influence that psychological factors and the surrounding social environment have on their physical and mental wellness and their ability to function. This approach is ...

dysfunction *

Anhedonia Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researchers t ...

* Depression * Impaired

interpersonal skills A social skill is any competence facilitating interaction and communication with others where social rules and relations are created, communicated, and changed in verbal and nonverbal ways. The process of learning these skills is called social ...

* Obsessive-compulsive behaviour * Feelings of guilt * Autonomic disturbances *

Pessimistic Pessimism is a negative mental attitude in which an undesirable outcome is anticipated from a given situation. Pessimists tend to focus on the negatives of life in general. A common question asked to test for pessimism is "Is the glass half empt ...

thoughts * Impaired

Attentional control Attentional control, colloquially referred to as concentration, refers to an individual's capacity to choose what they pay attention to and what they ignore. It is also known as endogenous attention or executive attention. In lay terms, attention ...

* Lack of initiative * Craving * Inability to think clearly * Memory problems * Emotional overreactions or numbness *

Sleep disturbances A sleep disorder, or somnipathy, is a medical disorder of an individual's sleep patterns. Some sleep disorders are severe enough to interfere with normal physical, mental, social and emotional functioning. Polysomnography and actigraphy are test ...

* Extreme fatigue * Physical coordination problems * Stress sensitivity * Increased sensitivity to pain *

Panic disorder Panic disorder is a mental disorder, mental and Abnormal behavior, behavioral disease#Disorder, disorder, specifically an anxiety disorder characterized by reoccurring unexpected panic attacks. Panic attacks are sudden periods of intense fear th ...

Psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

Generalized anxiety disorder Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...

* 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: * Stressful and/or frustrating situations * Multitasking * Feelings of

anxiety Anxiety is an emotion which is characterized by an unpleasant state of inner turmoil and includes feelings of dread over anticipated events. Anxiety is different than fear in that the former is defined as the anticipation of a future threat wh ...

fearfulness Fear is an intensely unpleasant emotion in response to perceiving or recognizing a danger or threat. Fear causes physiological changes that may produce behavioral reactions such as mounting an aggressive response or fleeing the threat. Fear i ...

anger Anger, also known as wrath or rage, is an intense emotional state involving a strong uncomfortable and non-cooperative response to a perceived provocation, hurt or threat. A person experiencing anger will often experience physical effects, su ...

* 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 Benzodiazepine withdrawal syndrome often abbreviated to benzo withdrawal or BZD withdrawal is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines, either medically or recreationally develops a phy ...

. 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 Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. Introdu ...

with

psychotic Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

features, including persistent depressed mood, poor concentration, decreased

appetite Appetite is the desire to eat food items, usually due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regu ...

insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...

anhedonia Anhedonia is a diverse array of deficits in hedonic function, including reduced motivation or ability to experience pleasure. While earlier definitions emphasized the inability to experience pleasure, anhedonia is currently used by researchers t ...

, anergia and

psychomotor retardation Psychomotor may refer to: * Psychomotor learning, the relationship between cognitive functions and physical movement * Psychomotor retardation, a slowing-down of thought and a reduction of physical movements in an individual * Psychomotor agitatio ...

. 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. 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 Depersonalization can consist of a detachment within the self, regarding one's mind or body, or being a detached observer of oneself. Subjects feel they have changed and that the world has become vague, dreamlike, less real, lacking in significa ...

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

, left temporal lobe EEG spiking activity,

hallucinations A hallucination is a perception in the absence of an external stimulus that has the qualities of a real perception. Hallucinations are vivid, substantial, and are perceived to be located in external objective space. Hallucination is a combinatio ...

, visual perceptual and sensory distortions which persisted for years. A clinical trial of patients taking the benzodiazepine alprazolam (

Xanax Alprazolam, sold under the brand name Xanax, among others, is a fast-acting, potent tranquilizer of medium duration in the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It is most commonly ...

) for eight weeks triggered protracted symptoms of memory deficits which were still present after up to eight weeks post cessation of alprazolam.

Dopamine agonist protracted withdrawal

After long-term use of

dopamine agonist A dopamine agonist (DA) is a compound that activates dopamine receptors. There are two families of dopamine receptors, D2-like and D1-like, and they are all G protein-coupled receptors. D1- and D5-receptors belong to the D1-like family and the ...

s, a

withdrawal syndrome 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. In order for the symptoms of wit ...

may occur during dose reduction or discontinuation with the following possible side effects: anxiety, panic attacks,

dysphoria Dysphoria (; ) is a profound state of unease or dissatisfaction. It is the semantic opposite of euphoria. In a psychiatric context, dysphoria may accompany depression, anxiety, or agitation. In psychiatry Intense states of distress and unea ...

, depression, agitation, irritability, suicidal ideation, fatigue,

orthostatic hypotension Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a person's blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hyp ...

, nausea, vomiting,

diaphoresis Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distribut ...

, 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.

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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neur ...

and resultant hyperexcitability of neuronal pathways. However, data supports "neuronal and overwhelming cognitive normalization" in regards to chronic amphetamine use and PAWS. 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. People with longer term and heavier substance use have caused damage to the nervous system, where, after cessation of the primary addictive substance, the opioid receptors may become favorable to any potential agonist. This places people with longer term and heavier substance use at risk of becoming addicted to any other agonist with very little use of the secondary agonist. Abstinence from all agonists, sometimes taking multiple years, is required for full recovery.

Flumazenil Flumazenil (also known as flumazepil, code name Ro 15-1788) is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines ( ...

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. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.

Acamprosate Acamprosate, sold under the brand name Campral, is a medication used along with counselling to treat alcohol use disorder. For label updates seFDA index page for NDA 021431/ref> Acamprosate is thought to stabilize chemical signaling in the brai ...

has been found to be effective in alleviating some of the post acute withdrawal symptoms of alcohol withdrawal.

Carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medi ...

trazodone Trazodone, sold under many brand names, is an antidepressant medication. It is used to treat major depressive disorder, anxiety disorders, and difficulties with sleep. The medication is taken orally. Common side-effects include dry mouth, fe ...

may also be effective in the treatment of post acute withdrawal syndrome in regards to alcohol use.

Cognitive behavioral therapy Cognitive behavioral therapy (CBT) is a psycho-social intervention that aims to reduce symptoms of various mental health conditions, primarily depression and anxiety disorders. CBT focuses on challenging and changing cognitive distortions (suc ...

can also help the post acute withdrawal syndrome especially when cravings are a prominent feature.

References