After substance withdrawal, underlying psychiatric symptoms emerge

When treating patients who abuse substances, it is important to watch for underlying clinical conditions that have been sup­pressed, relieved, or muted by alcohol or drugs. Many of these conditions can be mistaken for signs of withdrawal, drug-seeking, or new conditions arising from loss of euphoria from the drug. Prompt recogni­tion of these disorders and use of appropriate non-addictive treatments can prevent “against medical advice” discharges, relapses, and unneeded suffering in many cases.

Because the brain is the target organ, these conditions are either neuro­logic or psychiatric in nosology. Although psychiatric clinicians might not be familiar with neurologic conditions, quick recognition and treatment is necessary.

Restless legs syndrome and periodic limb movements of sleep
Restless legs syndrome (RLS) has 2 key components: paresthesia and akathisia. Although primarily involving the lower extremities, involve­ment also can include the upper extremities, torso, and head.

Paresthesia differs from typical neuropathies in that it usually is not pain­ful; rather, patients describe an odd sensation using terms such as ticklish, “creepy-crawly,” and other uncomfortable sensations.

Akathisia is a motor restlessness and need to move. The patient might feel momentary relief by moving or rubbing the extremities, only to have the paresthesia return quickly followed by the akathisia. Generally, reclining is the most prominent position that produces symptoms, but they can occur while sitting.

The cause of RLS is an abnormality of central dopamine or iron, or both, in the sub­stantia nigra; iron is a cofactor in dopamine synthesis. All RLS patients should have a serum ferritin level drawn and if <50 μg/dL, be treated with iron supplementation. Dopamine agonists, such as ropinirole, pramipexole, and carbidopa/levodopa, are effective (Table 1); other useful agents include benzodiazepines such as clonaz­epam and opioids such as hydrocodone.

When a patient withdraws from benzo­diazepines or narcotics, RLS can emerge and cause suffering until it is diagnosed and treated. Typical myalgia in opioid withdrawal can confound the diagnosis. The immediate-release (IR) and extended-release (ER) formu­lations of gabapentin often are a good choice when treating benzodiazepine or narcotic withdrawal. The side effect profile of gaba­pentin is relatively benign, with somnolence often reported by non-substance abusers, but it is unlikely that addicts, who have grown tolerant to more potent agents such as ben­zodiazepines and opioids, will complain of sleepiness. Studies have shown that gabapen­tin is useful in managing withdrawal as well as anxiety and insomnia.^1,2 A randomized trial showed that gabapentin increases abstinence rates and decreases heavy drinking.² The agent has a short half-life (5 to 7 hours); the IR form needs to be dosed at least 3 times a day to be effective. An ER formulation of gabap­entin was released in 2013 with the sole indi­cation for RLS.

Gabapentin is not significantly metabo­lized by the liver, has a 3% rate of protein bind­ing, and is excreted by the kidneys—making it safe for patients who abuse alcohol or opi­oids and have impaired hepatic function. Typical starting dosages of IR gabapentin are 100 to 300 mg, 3 times daily, if symptoms are present in the daytime. Asymmetric dosing can be helpful, with larger or single dosages given at bedtime (eg, 100 mg in morning, 100 mg in afternoon, 300 mg at bedtime). Dosing varies from patient to patient, from 300 mg to 3,600 mg/d. Increasing dosages produce lower bioavailability because of saturation in absorption or at the blood-brain barrier. At 100 mg every 8 hours, bioavail­ability is 80% but at 1,600 mg every 8 hours it drops to 27%.³

Periodic limb movements of sleep (PLMS) essentially is akathisia during sleep, and occurs in most patients with RLS. The patient feels tired in the morning because of lack of deep stage-N3 sleep. Because of the inverse relationship between serotonin and dopamine, most selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors can exacerbate RLS and PLMS.^4,5 Other culprits include antipsychot­ics, antiemetics, and antihistamines. The differential diagnosis includes withdrawal from opioids and attention-deficit/hyper­activity disorder (ADHD), which may be comorbid with RLS. There are many causes of secondary RLS including renal failure, pregnancy, varicose veins, and neuropathy.

Tremor
Benign familial, or essential, tremor is a fine intention tremor that can be suppressed by alcohol or benzodiazepines. After detoxifica­tion from either of these substances, persis­tent tremor can re-emerge; often, it is benign, although cerebellar and parkinsonian trem­ors must be ruled out. Essential tremor can be treated with gabapentin or beta blockers such as propranolol or metoprolol (Table 2).

Anxiety and panic disorder
Social anxiety often presents in addiction treatment centers in the context of group therapy, speaking in 12-step meetings, and having the patient describe his (her) autobi­ography and history of addiction. Because social anxiety disorder is the third most com­mon psychiatric disorder after simple pho­bia and major depressive disorder,⁶ it is not surprising that it emerges after withdrawal.