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

alcohol Alcohol may refer to: Common uses * Alcohol (chemistry), a class of compounds * Ethanol, one of several alcohols, commonly known as alcohol in everyday life ** Alcohol (drug), intoxicant found in alcoholic beverages ** Alcoholic beverage, an alco ...

opioid Opioids are a class of Drug, drugs that derive from, or mimic, natural substances found in the Papaver somniferum, opium poppy plant. Opioids work on opioid receptors in the brain and other organs to produce a variety of morphine-like effects, ...

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

barbiturate Barbiturates are a class of depressant, depressant drugs that are chemically derived from barbituric acid. They are effective when used medication, medically as anxiolytics, hypnotics, and anticonvulsants, but have physical and psychological a ...

s, and other substances. Infants born to mothers who used substances of dependence during pregnancy may also experience a PAWS. While PAWS has been frequently reported by those withdrawing from opioid and alcohol dependence, the research has limitations. Protracted benzodiazepine withdrawal has been observed to occur in some individuals prescribed benzodiazepines. 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.

Benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

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

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 PAWS 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 researcher ...

* 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 socia ...

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

Pessimistic Pessimism is a 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 empty or half ...

thoughts * Impaired attentional control * Lack of initiative * Craving * Inability to think clearly * Memory problems * Emotional overreactions or numbness *

Sleep disturbances Sleep is a state of reduced mental and physical activity in which consciousness is altered and certain sensory activity is inhibited. During sleep, there is a marked decrease in muscle activity and interactions with the surrounding environme ...

* Extreme fatigue * Physical

coordination Coordination may refer to: * Coordination (linguistics), a compound grammatical construction * Coordination complex, consisting of a central atom or ion and a surrounding array of bound molecules or ions ** A chemical reaction to form a coordinati ...

problems * Stress sensitivity * Increased sensitivity to pain *

Panic disorder Panic disorder is a mental 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 ...

Psychosis In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or inco ...

Generalized anxiety disorder Generalized anxiety disorder (GAD) is an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily functioning. Individuals with GAD are often overly con ...

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

anxiety Anxiety is an emotion characterised by an unpleasant state of inner wikt:turmoil, turmoil and includes feelings of dread over Anticipation, anticipated events. Anxiety is different from fear in that fear is defined as the emotional response ...

fearfulness Fear is an unpleasant emotion that arises in response to perceived dangers or threats. Fear causes physiological and psychological changes. It may produce behavioral reactions such as mounting an aggressive response or fleeing the threat, com ...

anger Anger, also known as wrath ( ; ) or rage (emotion), 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 experie ...

* 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 (BZD withdrawal) 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 stop ...

. 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 depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...

with

psychotic In psychopathology, psychosis is a condition in which a person is unable to distinguish, in their experience of life, between what is and is not real. Examples of psychotic symptoms are delusions, hallucinations, and disorganized or incoher ...

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 reg ...

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

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 researcher ...

, anergia and

psychomotor retardation Psychomotor retardation involves a slowing down of thought and a reduction of physical movements in an individual. It can cause a visible slowing of physical and emotional reactions, including speech and affect. Psychomotor retardation is most ...

. 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 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 Depersonalization is a dissociative phenomenon characterized by a subjective feeling of detachment from oneself, manifesting as a sense of disconnection from one's thoughts, emotions, sensations, or actions, and often accompanied by a feeling of ...

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

, left temporal lobe EEG spiking activity,

hallucinations A hallucination is a perception in the absence of an external stimulus that has the compelling sense of reality. They are distinguishable from several related phenomena, such as dreaming ( REM sleep), which does not involve wakefulness; pse ...

, 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 moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly prescribed in the ...

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

s, a

withdrawal syndrome 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 A drug is any chemical substance other th ...

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 uneas ...

, 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 they are standing up ( orthostasis) or sitting down. Primary orthostatic hypotension is also often referred to as ne ...

, nausea, vomiting,

diaphoresis Perspiration, also known as sweat, is the fluid secreted by 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 distributed over much of the ...

, 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, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotransmitters are rele ...

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.

Flumazenil Flumazenil, also known as flumazepil, is a selective GABAA receptor, GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (partic ...

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 which reduces cravings in alcoholism. It is thought to stabilize neurotransmission, chemical signaling in the brain that would otherwise be disrupted by alcohol withdrawal. When us ...

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

Carbamazepine Carbamazepine, sold under the brand name Tegretol among others, is an anticonvulsant medication used in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other medications and as ...

trazodone Trazodone is an antidepressant medication used to treat major depressive disorder, anxiety disorders, and insomnia. It is a phenylpiperazine compound of the serotonin antagonist and reuptake inhibitor (SARI) class. The medication is taken or ...

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 form of psychotherapy that aims to reduce symptoms of various mental health conditions, primarily depression, PTSD, and anxiety disorders. Cognitive behavioral therapy focuses on challenging and chang ...

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

References