DRUG TREATMENT OF WITHDRAWAL SYNDROMES Some general principles are important when considering phar-

macologic treatments for particular withdrawal syndromes: When monitoring treatment:

• set clear targets • make serial assessments and modify on the basis of these

assessments Psychosocial factors: • prepare the patient

• place emphasis on detoxification as a beginning to treatment

223 From a pharmacologic standpoint, an ideal agent for the treat-

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

ment of withdrawal should have the following characteristics: • efficacy in relieving the complete range of abstinence signs

and symptoms for a given type of withdrawal • a relatively long duration of action and gradual offset of effects • a high degree of safety in the dosage needed to suppress withdrawal (i.e., high therapeutic index) • it should be available by a variety of routes of administration and have little abuse potential in itself

Some equally general important aspects that may be over- looked include:

• keep clear treatment targets in mind • consider structured rating scales for measuring symptom

severity • treatment must be guided by serial assessment of the clinical response: protocols offer useful guidance but orders must be reviewed and rewritten, frequently daily. It is dangerous to detoxify a patient on autopilot

From the patient’s perspective: • they should be told what to expect from the experience of

detoxication • physicians should make the effort to engage them in a joint effort to alleviate symptoms safely • they should be awarae that they are unlikely to be free of distress • it may be possible to accomplish detoxication on an outpa- tient basis for those who have relatively good health and sufficient social stability

• most importantly, they must understand that detoxication is the beginning of treatment of their chronic problems with substance dependence – it is not, by itself, a treatment for

addiction

Alcohol Withdrawal Alcohol withdrawal symptoms typically occur 6–12 h after the

end of, or a reduction in, heavy and prolonged drinking;

224 HANDBOOK OF PSYCHIATRIC DRUGS

they may also occur despite the presence of significant blood alcohol levels if those levels are falling.

Alcohol withdrawal symptoms include: • autonomic hyperactivity

• increased muscle tremor (may affect the hand, eyelids, or tongue)

• insomnia • nausea or vomiting • transient hallucinations or illusions • agitation • anxiety

The alcohol withdrawal syndrome also includes generalized seizures. These may occur 12–48 h after the end of alcohol consumption; they are typically nonfocal and confined to one or two episodes.

Alcohol withdrawal delirium (delirium tremens) usually occurs 3–5 days after the end of consumption. This is associated with:

• disturbance of consciousness • change in cognition • perceptual disturbance • agitation, belligerence, and elevation in vital signs may

also occur This delirium is more likely to occur in the presence

of a comorbid physical disorder or in someone with a history of seizures or delirium during previous withdrawal syndromes. The occurrence of delirium is therefore an indi- cation for reassessing the patient’s medical status to identify possibly undiagnosed illness. Alcohol withdrawal is a medical emergency and can be life threatening without appropriate supportive medical treatment.

Appropriate management greatly reduces the risk that uncomplicated withdrawal will progress to seizures or delirium. Patients should undergo systematic assessment when they begin detoxication and during the process. The Clinical Insti- tute Withdrawal Assessment for alcohol scale is a simple tool that is widely used (Table 8-1).

225 Clinical Institute Withdrawal Assessment for Alcohol

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

Scale ∗

Patient: _________________ Time: ____: ____ (24 hour clock, midnight = 00:00) Date: ___ /___ /___

y m d NAUSEA AND VOMITING: Ask, “Do you feel sick to your stomach?

Have you vomited?” Observation. 0—no nausea and no vomiting 1—mild nausea with no vomiting 2 3 4—intermittent nausea with dry heaves 5 6 7—constant nausea, frequent dry heaves and vomiting

TREMOR: Arms extended and fingers spread apart. Observation. 0—no tremor 1—not visible, but can be felt fingertip to fingertip 2 3 4—moderate, with patient’s arms extended 5 6 7—severe, even with arms not extended

PAROXYSMAL SWEATS: Observation. 0—no sweat visible 1—barely perceptible sweating, palms moist 2 3 4—beads of sweat obvious on forehead 5 6 7—drenching sweats

Pulse or heart rate, taken for 1 minute: ___________________ Blood pressure: ____ /____

TACTILE DISTURBANCES: Ask, “Have you any itching, pins-and-needles sensations, any burning, any numbness, or do you feel bugs crawling on or under your skin?” Observation. 0—none 1—very mild itching, pins and needles, burning, or numbness

226 HANDBOOK OF PSYCHIATRIC DRUGS

(Continued) 2—mild itching, pins and needles, burning, or numbness

3—moderate itching, pins and needles, burning, or numbness 4—moderately severe hallucinations 5—severe hallucinations 6—extremely severe hallucinations 7—continuous hallucinations

AUDITORY DISTURBANCES: Ask, “Are you more aware of sounds around you? Are they harsh? Do they frighten you? Are you hearing anything that is disturbing to you? Are you hearing things that you know aren’t there?” Observation. 0—not present 1—very mild harshness or ability to frighten 2—mild harshness or ability to frighten 3—moderate harshness or ability to frighten 4—moderately severe hallucinations 5—severe hallucinations 6—extremely severe hallucinations 7—continuous hallucinations

VISUAL DISTURBANCES: Ask, “Does the light appear to be too bright? Is its color different? Does it hurt your eyes? Are you seeing anything that is disturbing you? Are you seeing things that you know aren’t there?” Observation. 0—not present 1—very mild sensitivity 2—mild sensitivity 3—moderate sensitivity 4—moderately severe hallucinations 5—severe hallucinations 6—extremely severe hallucinations 7—continuous hallucinations

ANXIETY: Ask, “Do you feel nervous?” Observation. 0—no anxiety, at ease 1—mildly anxious 2 3 4—moderately anxious, or guarded, so anxiety is inferred 5 6 7—equivalent to acute panic states as seen in severe delirium or acute schizophrenic reactions

AGITATION: Observation. 0—normal activity 1—somewhat more than normal activity

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

2 3 4—moderately fidgety and restless 5 6 7—paces back and forth during most of the interview, or constantly thrashes about

HEADACHE, FULLNESS IN HEAD: Ask, “Does your head feel different? Does it feel like there is a band around your head?” Do not rate dizziness or lightheadedness. Otherwise, rate severity. 0—not present 1—very mild 2—mild 3—moderate 4—moderately severe 5—severe 6—very severe 7—extremely severe

ORIENTATION AND CLOUDING OF SENSORIUM: Ask, “What day is this? Where are you? Who am I?” 0—oriented and can do serial additions 1—cannot do serial additions or is uncertain about date 2—disoriented for date by no more than 2 calendar days 3—disoriented for date by more than 2 calendar days 4—disoriented for place and/or person

Total CIWA-A score ____ Rater’s initials ____ Maximum possible score—67

∗ This scale is not copyrighted and may be used freely. See Sullivan JT, Sykora K, Schneiderman J, Narango CA, Sellers EM (1989).

Assessment of alcohol withdrawal: the revised Clinical Institute Withdrawal Instrument for Alcohol Scale (CIWA-AR). British Journal of Addiction 84:1353–1357.

The scale should be administered at regular intervals (initially every 1–2 h) 6–24 h after the patient’s last drink until there are at least two consecutive assessments with scores less than 8–10; structured assessment can then safely end. Closer monitoring is indicated if the score exceeds 15; the interpreta- tion of intermediate scores depends on clinical judgment, taking into account issues such as the history of withdrawal episodes and the degree of discomfort experienced by the patient.

228 HANDBOOK OF PSYCHIATRIC DRUGS

Provided serial clinical assessments are carried out, it is relatively straightforward to strike a balance between withdrawal and intoxication. The most common error associated with drug treatment of withdrawal is prescribing doses that are too small or dose intervals that are too long.

Benzodiazepines are the treatment of choice for alcohol withdrawal. They are relatively safe compared with other sedative–hypnotic drugs; and they reduce the frrequency of seizures and delirium. Alcoholics are cross-tolerant to their effects and may therefore require doses that would be consid- ered high for non-tolerant individuals.

The benzodiazepines can be dividied into two classes according to their duration of action:

• Longer-acting agents include chlordiazepoxide (which has lower abuse potential and may therefore be preferred) and diazepam. These agents undergo both oxidation and glucuronidation. It is an advantage that blood levels of these agents decline gradually during the tapering process because this is associated with greater between-dose patient comfort and possibly better seizure prophylaxis. The disadvantage is that if elimination is delayed (for example, in elderly patients or patients with impaired liver or pulmonary function), there is a risk that accumulation will cause toxicity.

• Shorter-acting agents include oxazepam and lorazepam, which undergo only glucuronidation. Their advantage is that they are well metabolized and eliminated by elderly people, with less chance of accumulation and toxicity in patients with liver disease. The disadvantage is that between-dose blood levels may decline abruptly, increasing the risk of break- through symptoms and seizures.

All may be administered orally or intravenously; only lorazepam is available as an intramuscular injection. The patient’s response should be determined by serial assessments and drug treatment should be adjusted according to clinical need. For example, increasing signs of withdrawal indicate the need for an increase in dose or a decrease in the

229 dose interval. A degree of sedation is desirable but if over-

DRUGS FOR TREATING SUBSTANCE ABUSE DISORDERS

sedation occurs drug treatment should be withheld until it is again clinically indicated. Recommendations for medication are summarized in Figure 8-1.

Hallucinations that develop during delirium are relatively refractory to benzodiazepines alone; if they occur despite substitution therapy with a sedative–hypnotic, adjunctive haloperidol 2–5 mg may be administered.

If persistent tachycardia or hypertension occur the possi- bility should be excluded that they may be due to inadequately treated withdrawal. Treatment with a beta-blocker or cloni- dine has been successful; these agents may also decrease vital signs and tremor but they do not prevent seizures.

As an alternative management strategy, a patient attending for detoxication may be ‘frontloaded’ with 1–2 hourly doses of diazepam or chlordiazepoxide to achieve sedation. Because

Patient in Alcohol Withdrawal

<65 years old and no evidence >65 years old or evidence of of liver or pulmonary dysfunction

liver or pulmonary dysfunction

Day 1: Day 1:

Chlordiazepoxide, 50–100 mg q6h Lorazepam, 2 mg q4h

Day 2: Day 2:

Chlordiazepoxide, 50–100 mg q8h Lorazepam, 1.5 mg q4h

Day 3: Day 3:

Chlordiazepoxide, 50–100 mg q12h Lorazepam, 1 mg q4h

Day 4: Day 4:

Chlordiazepoxide, 50–100 mg hs Lorazepam, 0.5 mg q4h FIGURE 8-1. Medication recommendations for treating alcohol

230 HANDBOOK OF PSYCHIATRIC DRUGS

these drugs have a long elimination half-life, their effects diminish slowly over the period of withdrawal. However, the need remains for careful serial assessment while there is a risk of withdrawal complications.

Reports of experience with carbamazepine and valproate in the treatment of alcohol withdrawal are promising and they may have a role in special circumstances. However, the safety and efficacy of benzodiazepines is currently unsurpassed.

Thiamine is indicated for every patient with alcoholism to prevent Wernicke’s encephalopathy and Korsakoff’s amnestic syndrome. The typical dose is 100 mg/day; replacement with thiamine should begin immediately and must precede administration of intravenous glucose. Nutritional management is completed with the addition of folate and multivitamin supplements, though the need is less acute. Although some believe that magnesium supplementation prevents withdrawal seizures, there is no consensus on its role in the absence of proven magnesium deficiency.

DRUG TREATMENT OF WITHDRAWAL SYNDROMES Some general principles are important when considering phar-