Opioid withdrawal

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2]

Overview

Opioid withdrawal occurs due to the cessation of opioids or the administration of an opioid antagonist following a heavy or prolonged use of opioids. Symptoms of withdrawal from opiates include, but are not limited to, depression, aggression and irritability, leg cramps, abdominal cramps, vomiting, diarrhea, insomnia, and cravings for the drug itself. Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days.

Historical Perspective

• Opium and its derivatives have been used as medical therapies since 5,000 years ago.
• In the United States, in the early 20th century, opiates were over-the-counter drugs and were commonly used in medical therapy of various disorders.
• In the early 1900s, the federal restrictions on opioid access caused suffering and death since there were no effective treatments for the opioid withdrawal symptoms that happened with sudden discontinuation of opioids.

Classification

The onset and duration of opioid withdrawal depends on the half-life of the consumed opioid:

Half-lives of Opioids	Onset of Withdrawal Symtoms	Duration of the syndrome
Short half-lives eg, heroin at 3–5 h	Within 12 h of last use	eg, heroin withdrawal lasts 4–5 days
Long half-lives eg, methadone at up to 96 h	1–3 days after last use	Methadone withdrawal lasts 7–14 days Some last for several weeks

Causes

Opioid withdrawal may be caused by discontinuation of repeated use of an opioid.

Differentiating opioid withdrawal from other diseases and conditions

Opioid withdrawal must be differentiated from:

• Sedative-hypnotic withdrawal
• Hallucinogen intoxication
• Stimulant intoxication
• Opioid-induced depressive disorder

Disease	Prominent clinical features	Investigations
Hyperthyroidism	The main symptoms include: Palpitations Insomnia Anxiety Weight loss Heat intolerance Diarrhea Depending on the underlying diagnosis, the patient might have exophthalmus or goiter	The patient usually has elevated T3 and T4 TSH might be increased or decreased depending on the underlying cause Thyroid stimulating antibodies (TSI) might be increased in cases of Graves’ disease
Essential hypertension	Most patients with hypertension are asymptomatic at the time of diagnosis. Common symptoms are listed below: Headache Blurry vision Dyspnea Epistaxis Tinnitus Fatigue Drowsiness	JNC 7 recommends the following routine laboratory tests before initiation of therapy for hypertension: 12-Lead electrocardiogram (ECG) Urinalysis, including urinary albumin excretion or albumin/creatinine ratio Blood glucose Blood hematocrit Serum electrolytes, especially potassium Serum calcium Lipid profile: Total cholesterol, LDL, HDL, triglycerides Creatinine or estimated GFR
Generalized anxiety disorder	According to DSM V, the following criteria should be present to fit the diagnosis of generalized anxiety disorder: The presence of sense of apprehension or fear toward certain activities for most of the days for at least 6 months Difficulty to control the apprehension Associated restless, fatigue, irritability, difficult concentration, muscle tension or sleep disturbance (only one of these manifestations) The anxiety or the physical manifestations must affect the social and the daily life of the patient Exclusion of another medical condition or the effect of another administered substance Exclusion of another mental disorder causing the symptoms	-
Menopause	The perimenopausal symptoms are caused by an overall drop, as well as dramatic but erratic fluctuations, in the levels of estrogens, progestin, and testosterone. Some of these symptoms such as formication etc may be associated with the hormone withdrawal process. Vasomotor instability in the form of hot flushes, including night sweats and sleep disturbances Urogenital atrophy causing itching, dryness, bleeding, watery discharge, urinary frequency, urinary urgency and urinary incontinence Skeletal symptoms in the form of osteoporosis (gradually developing over time), artharlgia, myalgia and back pain Psychological manifestations such as mood disturbance, irritability, fatigue, memory loss and depression Sexual disorders: decreased libido, vaginal dryness, problems reaching orgasm and dyspareunia	B-HCG should always be done first to rule out pregnancy especially in women under the age of 45 years FSH can be measured but it can be falsely normal or low TSH, T3 and T4 to rule out thyroid abnormalities Prolactin can be measured to rule out prolactinoma as a cause of menopause
Opioid withdrawal disorder	According to DSM V, the following criteria should be present to fit the diagnosis of opioid withdrawal: Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer) or administration of an opioid antagonist after a period of opioid use. Development of three or more of the following criteria minutes to days after cessation of drug use: dysphoric mood, nausea or vomiting, muscle aches, Lacrimation or rhinorrhea, pupillary dilation, piloerection, or sweating, diarrhea, yawning, fever, and insomnia. The signs or symptoms mentioned above must cause impairment of the daily functioning of the patient. The signs or symptoms mentioned above must not be attributed to other medical or mental disorders.	Urine drug screen to rule out any other associated drug abuse Routine blood work such as electrolytes and hemoglobin to rule out any associated disease explaining the symptoms
Pheochromocytoma	The hallmark symptoms of a pheochromocytoma are those of sympathetic nervous system hyperactivity, symptoms usually subside in less than one hour and they may include: Palpitations especially in epinephrine producing tumors. Anxiety often resembling that of a panic attack Sweating Headaches occur in 90 % of patients. Paroxysmal attacks of hypertension but some patients have normal blood pressure. It may be asymptomatic and discovered by incidence screening especially MEN patients. Please note that not all patients with pheochromocytoma experience all classical symptoms.	Diagnostic lab findings associated with pheochromocytoma include: Elevated plasma and urinary catecholamines and metanephrines Elevated urinary vanillyl mandelic acid

Epidemiology and Demographics

Prevalence

The prevalence of opioid withdrawal is 6,000 per 100,000 (60%) of the population that have used heroin one or more time in the prior 12 months.

Risk Factors

Opioid withdrawal may be caused by discontinuation of repeated use of an opioid in any setting such as:

• Medical therapy of pain
• Opioid agonist therapy for opioid use disorder
• Recreational use
• Self-treating the symptoms of mental disorders

Natural History, Complications and Prognosis

Depending on the quantity, type, frequency, and duration of opioid use, the physical withdrawal symptoms last for as little as 5 days and as much as 14 days. The user, upon returning to the environment where they usually used opiates, can experience environmentally implied physical withdrawal symptoms well-after regaining physical homeostasis - or the termination of the physical withdrawal phase by synthesis of endogenous opioids (endorphins) and upregulation of opioid receptors to the effects of normal levels of endogenous opioids. These implied symptoms are often just as distressing and painful as the initial withdrawal phase.

Detoxification is best conducted in an in patient facility that provides a controlled environment. Patients who are isolated and exposed solely to care givers and other patients in this environment have a better rate of staying clean then those who detox out-patient.

Diagnosis

Diagnostic Criteria

DSM-V Diagnostic Criteria for Opioid Withdrawal

“

A. Presence of either of the following; 1. Cessation of (or reduction in) opioid use that has been heavy and prolonged (i.e.,several weeks or longer). 2. Administration of an opioid antagonist after a period of opioid use. AND B. Three (or more) of the following developing within minutes to several days after Criterion A: 1. Dysphoric mood. 2. Nausea or vomiting. 3. Muscle aches. 4. Lacrimation or rhinorrhea. 5. Pupillary dilation, piloerection, or sweating. 6. Diarrhea. 7. Yawning. 8. Fever. 9.Insomnia. AND C. The signs or symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. AND D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication or withdrawal from another substance.

”

History and Symptoms

The most common symptoms of opioid withdrwal include :

• Anxiety
• Anxiety
• Restlessness
• Irritability
• Insomnia
• Hot flashes
• Chills
• Sweating
• Pupillary dilatation
• Heart pounding
• Lacrimation
• Rhinorrhea
• Yawning
• Gooseflesh
• Nausea, vomiting
• Abdominal cramps
• Diarrhea
• Aches, pain
• Muscle spasms, twitching
• Tremor

Physical Examination

Common physical examination findings of opioid withdrwal include:

• Anxiety
• Restlessness
• Irritability
• Hypertension
• Tachycardia
• Mydriasis
• Piloerection (such as goose bumps)
• Lacrimation
• Rhinorrhea
• Yawning
• Nausea, vomiting
• Diarrhea
• Sweating
• Muscle spasms, twitching
• Tremor