51. Sedative-Hypnotic Drugs

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Sedative-Hypnotic Drugs 271start a person on an antidepressant along with a benzodiazepine, and then later discontinue the ben-zodiazepine.

BIBLIOGRAPHY1. Keck PE, McElroy SL: New uses for antidepressants:Social phobia. J Clin Psychiatry 58(Suppl 14):32-36, 1997.2. Pies RW: Handbook of Essential Psychophannacology.Washington DC, Ainerican Psychiatric Press, Inc., 1998.3 . SchatzhergAF Nemeroff CB: Textbook of Psychopharmacology, 2nd ed. Washington, DC, American4. SchnabelT: Evaluation of the safety and side effects of antianxiety agents.Am J Med 82:7-13, 1987.5. Schweizer E: Generalized anxiety disorder: Longitudinal course and pharmacoiogic treatment. Psychiatr ClinNorth Am 18(4):843-857, 1995.6. Uhlenhuth EH, Baiter MB, Ban TA,Yang K: Internationalstudy of expert judgment on therapeutic use of ben-zodiazepines and other psychotherapeutic medications: V. Treatment strategies in panic disorder,1992-1997. Clin Psychopharm 18(6 Suppl2):27S-31S, 1998.

Psychiatric Press, Iuc., 1998.

5 1 . SEDATIVE-HYPNOTIC DRU GSKim Nagel, M . D .

1. What clinical situations provide clearcut indications for sedative-hypnotic drugs?Transient insomnia and recurrent transient insomnia are the only clearcut indications for seda-

tive-hypnotic drugs. Additional indications and longer-term use require careful clinical assessmentand weighing other treatment options.2. How is transient insomnia defined?

Transient insomnia is a period of insomnia usually 1-14 days in length and often in response toa specific stressor (e.g., loss, illness, hospitalization, long-distance travel). After a duration of 3months, insomnia is considered to be subacute or chronic and requires further work-up to define un-derlying etiology.Case study: A 34-year-old woman presents 7 days after the unexpected death of her father. Shereports trouble getting to sleep before 2-2:30 AM, difficulty arising for work in the morning, and day-time fatigue. Although sad, she reports few vegetative signs of depression. She is given 20 tablets ofzolpidem, 10 mg, to use as needed over the next 3-4 weeks. At follow-up she says that she took themedication nightly with good response and ran out 3 days before her appointment. She has slept onlyapproximately5 hours for the last 3 nights off medication and feels that continuing it would be helpful.A few times in the last week she woke up early and was unable to return to sleep, but overall she feelsthat her mood is good. Two additional refills of zolpidem, 10mg, are given with follow-up as needed.

Her next visit occurs in 8 weeks, and she reports that early morning awakening has becomemore frequent. Occasionally she takes an additional one-half pill to get back to sleep at 3:OO A M .When she ran out of pills, sleep became much more difficult and impairment of concentration atwork became more noticeable. She says that she has lost weight and feels less enthusiasm. Major de-pression is diagnosed, and sertraline is started at 50 mg and increased to 100 mg the next week. Fourweeks after starting sertraline, her sleep returns to normal, and she stops zolpidem on her own. Atthis point she agrees that weekly psychotherapy would be beneficial to deal with issues arising fromher fathers death and that continuing sertraline is appropriate at this time.3. What is the recommended treatment for transient insomnia?

A consensus paper published by the National Institute of Mental Health (NIMH) in 1984 statedthat benzodiazepines (and closely related compounds) are the first choice of medication for transientinsomnia because of safety, efficacy, and side-effect profiles. The consensus recommended use ofthe lowest possible dose for the shortest period of time until insomnia improves, with a maximum of20 dosedmonth for 3 months.


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272 Sedative-Hypnotic Drugs4. Why is it important to avoid long-term use of sedative-hypnotic medication?Long -term use of hypnotics sho uld be avoided for several reasons. First, many cas es of insom -nia are truly transient, and patients need to be informed clearly that brief treatment may be adequate.Some patients develop a habit of regular sedative usage; when they stop, the may be disturbed by

brief rebound insom nia and believe that they m ust stay on medication. Tolerance, which tends to de-velop to most sedatives over time, decreases their efficacy and may promote escalation of dosage.All sedativekypn otics have side effects, including decreased dream ing and deep sleep and increasedbrief arousals at night, which m ake sleep less restful (see Qu estion 8). Even m ore important is thatlong-term symptomatic treatment of insomn ia may prevent the detection of an underlying m edical orpsychiatric condition that can be treated with better response.Although a num ber of conditions m ay benefit from long -term sedatives, it is important to diag-nose and treat them adequately. In general, nonaddictive agents are preferred to treat chronic insom-nia. Some studies have supported long-term use of nonbenzodiazepine hypnotics as a safe andeffective treatment. An open trial in France of 180 consecutive days of 10-20 mg of zolpidem fo r in-somnia showed little tolerance and virtually no withdraw al or rebound insomnia after discontinuation.5. What factors should be considered in deciding which hypnotic is most appropriate for a

specific patient?Assess the form of the patients insom nia. The four most comm on types of insom nia are:Sleep onset or initial insom niaFrequent short awakeningsOn e or two long awakeningsEarly morning awakening (early awakening is a comm on symptom in major depressive disorder)Assess pertinent characteristics of the sedative-hypnotic:Rate of absorptionExtent of distribution in body and CNSAffinity of CNS receptorsElimination half-lifeRoute of metabolic biotransformationFor the sake of simplification, rate of absorption and elim ination half-life can be used to gu idedrug choice.GABAABenzodiazepine Receptor Agonist Hypnotics

HALF-LIFE (HRS) ABSORPTION TYPICAL DOSAGEZaleplon (Sonata)Zolpidem (Ambien)Triazolam (H alcion)ZopicloneTemazepam (Restoril)Estazolam (Prosom)Oxazepam (Serax)Alprazolam (Xanax)Lorazepam (Ativan)Clonazepam (Klonipin)Quazepam (Doral)Flurazepam (Dalmane)

1-1.21 . 5 42-55-68-12

12-205-15

12-2010-2222-3850-20050-200

FastFastFastFastModerateModerateModerateFastModerateSlowFastFast

5-10 mg2.5-10 mg0.125-0.25 mg3.75-7.5 mg7.5-30 ing1-2 mg10-25 mg0.25-1 O mg0.5-2 mg0.5-2 mg7.5-15 mg15-30 mg

6. What drugs are most helpful for sleep onset or initial insomnia?If the patient has trouble falling asleep initially, zolpidem, triazolam , zaleplon, and temazepamare the best choices. Zolpidern is effective, rapidly ab sorbed, cleared quickly from the system, andthere is minimal evidence of m emory loss, motor incoordination, tolerance, or withdrawal symptoms.


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Sedative-Hyp notic Drugs 2 73Zaleplon 10 mg has the same rapid onset of action and rapid clearing . Its short duration of actionmay convey even less risk of impairing coordination or cognition.A number of studies have suggested that triazolam is equivalent in efficacy and side effects(except perhaps rebound insomnia) if not used above 0.25 mg. It is a reasonable next choice atone-third the price.The fourth choice is temazepam 15-30 mg, which is the least expensive of the four.Occasionally the three shorter-acting agents shift the patients sleep pattern from sleep-onset insom-nia to early mo rning aw akening after the drug is mostly cleared from the s ystem . Temazepamslonger duration of action m ay be helpful to combat this tendency. As temazepam is slowly absorbed,it may need to be taken I-1 hours before bedtime to aid getting to sleep. Elderly patients are gen-erally given one-half the average adult dosage.7. What drugs are most helpful for nocturnal and early morning awakening?Temazepam is the first choice for nocturnal and early morning awakenings. It is slowly ab-sorbed, but its peak effect begins about 1-1 2 hours after administration and persists for 6-10 hours.

Th is duration of action may be ideal to maintain sleep until morning without leaving the patientgroggy the next day. Depending on the patient, shorter-acting (triazolam, zolpidem) or longer-acting(estazolam, oxazepam, lorazepam, clonazepam ) may be m ore suitable.Th e long-acting drugs, such as flurazepam, quazepam , and chlorazepate, are quite effective fornocturnal and early morning awakening s, but the patient may hav e daytime hangover, memo ry loss, orincoordina tion. These dru gs are best for very anxious patients or for infrequent or intermittent usage.Zaleplon offers unique benefits. Three to four hours after ingestion, patients are nearly free ofimpaired cognition o r coordination; thus, depending on arising time, the patient may take zaleplonas late as 2-3 AM to return to sleep without fear of hangover. This allows the patient to take m edica-tion only if he or she needs it, rather than prophylactically at bedtime in case nocturnal or earlymorning awakening occurs.

8. What are the likely side effects of benzodiazepine receptor agonists?The m ost common side effects of benzod iazepine receptor agon ists are daytime seda tion, motor in-coordina tion, slow reaction times, anterograde and retrograde amnesia, confusional states, withdrawalstates, rebound insomnia, respiratory depression, tolerance to drug effect, and potential for abuse.9. With such side effects why are benzodiazepine receptor agonists the drugs of choice?They are easily tolerated by most patients and highly effective in 75-90 of cases. Side effectscan be minimized by d rug choice, regulation of dosage, and dosing schedules. One of the major ad -vantages is their safety in overdose. The lethal dose is so large for all benzodiazepine receptor ago-nists death is unlikely even from a whole m onths supply. A patient merely becom es highly sedateduntil the drug is cleared from the bloodstream.

10. What is anterograde amnesia? Discuss its cause and prevention.Anterograde amnesia is impaired consolidation of new memories of experiences or learning afteradministration of a drug. In contrast, retrograde am nesia is impaired recall of previous ly consolidatedmemo ry. Anterograde am nesia may occur wh en high doses of long-acting o r short-acting drugs areused. It generally is prevented by u sing as low a dose of a hypnotic as possible and avoiding concurren tusage of other drugs or alcoho l. High-p otency hypnotics are more likely to cause anterograde amnesia.11. What are the guidelines for prescribing to elderly patients or other groups that may sufferfrom impaired liver metabolism?For elderly patients or patients with liver impairment, very short-acting drugs such as triazolam,zaleplon, or zolpidem, or drugs that do not require hydroxylation by the liver, are preferred.Temazepam, lorazepam, and oxazepam are excreted by the kidneys without necessity of liver hy-droxy lation; therefore, their metabolism and excretion are not prolonged by age or liver dysfunction.Unexpected falls may be an unfortunate consequence of motor incoordination induced by hyp-notics used in the elderly. The weakened and brittle nature of their bones makes them highly prone


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2 74 Sedative-Hypnotic Drugsto hip fractures if they fall. The likelihood of hip fracture in the elderly may be correlated with thehalf-life of a regularly used hypnotic. One study showed that flurazepam is twice as likely as triazo-lam to cause a hip fractu re with regular use in elderly patients.12. What are the effects of sedativelhypnotic drugs on sleep quality?Benzodiazepine hypnotics generally increase total sleep time, tend to supp ress and delay RE Mor dreaming sleep , increa se the duration of stage 2 sleep, and decrease the amount of stage 3 and 4 ordeep sleep. Most users feel more refreshed a nd alert in the daytime compared w ith periods of in so m -nia but less rested than in period s of norm al, unmedicated sleep. Stopping such drug s after short orintermediate term usage may result in REM rebound (increase in REM sleep) and rebound insomniafor 0-3 days. Studies of zolpidem indicate that it increases total sleep time, increases deep sleep butdoes not suppress REM sleep or create REM rebound with discontinuation. Zaleplon decreases sleeplatency, increases deep sleep, but may decrease REM sleep. Correct doses of most benzodiazepinereceptor agonists enhance next day functioning.13. What is the mechanism of action of benzodiazepine and nonbenzodiazepine hypnotics?Both benzodiazepine and the new er nonbenzodiazep ine hypnotics have an inhibitory effect on thecentral nervous system that is med iated through the stimulation of benzod iazepine receptors creating anagonist effect on the neurotransmitter, gamm a-aminobutyric acid (GA BA). The G AB AA eceptor com-plex in the brain contains two benzodiazepine receptor subtypes: omega-1 0,) nd omega-2 w2).Agonistic stimulation of these receptors causes hyperpolarization of associated neural membranes whichdecreases the cells excitability or response to stimulus. Omeg a- 1 receptors seem to mediate sedation,whereas omega-2 receptors mediate anxiety reduction, anticonvulsant activity and, unfortunately,memory loss and m otor incoordination. Most b enzodiazepines stimulate both omega-1 and omega-2 re-ceptors; therefore, their sedative effect correlates with an adverse effect on coordination and m emory.Benzodiazepines typically stimulate a third receptor, omega-3 a3),ut these receptors are mostly lo-cated in the spinal cord and have no relevance to sleep, mem ory, or coordination. It should be that pa-tients will feel an improvem ent in well-being from use of a hypnotic withou t an objective response intotal sleep time. Changes in percep tion of sleep duration may be part of the drugs mode of action.14. Is it possible to create a drug with fewer side effects by stimulating only the benzodi-azepine omega-1 receptors?Theoretically, yes. At least three drugs have show n a pharm acological profile of selective bindingto omega- 1 receptors. These include quazepam, zolpidem, and zaleplon. Q uazepam itself is w,-selec-tive, but its two long-acting metabo lites are approximately 150 times more potent and not w,-selective.Zolpidem is wl-selective and has no sign ificant active metabolites. It has the theoretical advan tage ofw1selectivity but has no t been sho wn to have a statistically significant advantage in reduction of m otorincoordina tion or memory impairm ent over non-w, -selective, short-acting benzodiazep ines (e.g., tria-zolam) at typical therapeutic dosages. Evidence does suggest that zolpidem may offer a more physio-logically normal sleep, produce fewer withdrawa l symptom s, and be less prone to induce tolerance.Zaleplon is another nonbenzodiazepine sedative hypnotic with w, receptor selectivity. It differsfrom othe r short-acting seda tives in that its elimination half-life is only one hour. Stud ies have show nvery little effec t on cognition o r coordination at 3 A ours post ingestion. This implies the possibil-i ty of using zaleplon not on ly to treat sleep onset insom nia but also to treat nocturnal or early m orn-ing awakenings as long as there is still 4 hours till arising time.15. In addition to transient insomnia what other common diagnoses or conditions may bene-fit from the use of sedative-hypnotic agents?Chron ic insomnia due to:

Age. Ones ability to remain asleep decre ases with age. In severe cases, after enco urag ingphysical activity and sleep hygiene, the clinician may give a 2-week trial of zolpidem, 5 mg;triazolam, 0.125 mg, or temazepam, 7.5-15 mg. If the drug is clearly helpful and side effectsare not severe, it may be continued with attempts to shift to intermittent dosing if tolerancebegins to d evelop.


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Sedative-Hypnotic Drugs 275Chronic pain. Many nocturnal arousals from sleep are caused by pain. Tricyclic antidepressants(e.g., amitriptyline, 10 50 mg, dox epin, 10-50 mg) are first choices in patients w ith chronicpain, because they reduce pain sensations as well as frequency or duration of awaken ings.Chronic medical cond ition.Congestive heart failure i s an example of a chronic medical con-dition that induces severely fragmented sleep. Temazepam, 15 mg, has been shown to de-crease nighttime awakening and arousals and to improve daytime alertness with nocom prom ise of the medical condition.M edication side effects. For exam ple, in a 38-year-old asthmatic woman taking long-actingtheophylline (300 mg/day) and using a metapro terenol sulfate inhaler (2 puffs 4 t imedday),the stimulating effects of medication may induce severe insomnia and occasional symptomsof anxiety. Flurazepam , 15 mg, can be used at bedtime 3-6 timed we ek to inhibit insomniaand daytim e anxiety.Fibrom yalgia chronic fatigue syndrom e. First choices are doxepin, 10-50 mg at bedtime;amitriptyline, 10-50 mg at bedtime; or nortriptyline, 10-50 mg at bedtime (if anticholinergiceffect of doxepin or amitriptyline is too strong). Studies show that sleep improvement i s corre-lated with improvement in pain or fatigue in some patients. Patients who are intolerant of tri-cyclic antidepressants may consider trazodone, 25-1 00 mg, short-acting benzodiazepines, ormirtazapine, 15-60 mg qhs.Major depressionBipolar affective disorderDysthymic disorderPanic disorderGeneralized anxiety disorderPosttraumatic stress disorderPsychophysiologic insom nia. Th is is a conditioned negative response to ones sleep environ-

ment. Sleep hyg iene, sleep restriction, stimulus control, and relaxation training often are effective.Short-acting benzodiazepine receptor agonists may aid psychological intervention as well as low-dose sedating tricyclics or trazodone.Restless leg syndrom e. This crawling discomfort in the legs m akes one feel a need to stretch ormove the legs and causes sleep onset insomnia. It may be associated with iron or B 12 deficiencyanemia, renal disease, or pregnancy after week 20.Periodic leg movements of sleep. Leg-jerking movements accompany restless leg syndromebut also may occur up to 2-3 tim edm inu te during sleep in patients without restless leg sym ptom s.The arousals that they cause m ay m ake sleep nonrestorative.Recom mend ed order of treatment for restless leg syndro me and periodic leg m ovem ents isSinemet (th e combination of carbidopa [15 mg] and levodopa [lo0 mg]), 1-2 tablets at bedtime.(This works about 50 of the time but may induce nightmares.) If it fails, try an alternative dopamineagonist like bromocriptine or pergolide. Other alternatives include:Temazepam 15-30 mg at bedtimeClonazepam 0.5-2 mg at bedtimePercocet (the combination of oxycodone HCL and acetaminoph en), 1-2 tablets at bedtime.This m ay be the most effective treatment, but the add ictive nature of the dru g requires that theleg movements m ust be severe and documented by nocturnal polysomnogram. Studies haveshown that Percocet and other opia tes actually eliminate the leg-jerking movem ents ratherthan just allow the patient to s leep through the disturbance of the movem ent. Dos age can be

held steady for m any years without significant tolerance to benefits.Melatonin is a hormone created by the pineal gland at night in concert with the calm phase ofthe bodys daily rhythm . E vidence su gges ts that 1-2 tablets of 2.5-mg Melatonin given inearly afternoon help to maintain or reregulate an out-of-sync circadian rhythm.Triazolam 0.125-0.25 mg , or zolpidem , 5-10 mg, also may be used to help reestablish anormal circadian sleep pattern.Bright light therapy can be used to reset circadian rhythm.

Circa diadr hyth m disturbances


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Sedative-Hypnotic Drugs 77and agitated drug withdrawal states. Although responses can be varied, Neurontest (gabapentin100-200 mg) or Lomictal (lamotrigine 235-100 mg) can show distinctly sedative properties whichmay improve sleep and stabilization of bipolar disorder.20. What other drugs are of occasional usefulness as sedative-hypnotic agents?

Other Drugs With Sedative Hypnotic P ropertiesDRUG DOSAGE USES

AntihistaminesAllergies, mild insomnia, patients at risk to abuse medications,

patients on antipsychotic medication with extrapyramidalsymptoms such as muscle dystonia or parkinson-like remor

Posttraumatic stressdisorder, cluster headaches with insomnia,nightmares

Atypical Neuroleptics

Diphenhydramine 25-100 mg

Cyproheptadine 4 4 0 mg

Quetapine (Seroquel) 25-600 mgOlanzapine (Zyprexa) 2.5-20 mgRisperidine (Risperdal) 0.9-10 mg

First-line treatments for psychotic disorders; often useful inbipolar disorder or in borderline personality disorder; atypical neuroleptics commonly used for insomnia, agitation,or paranoia in elderly demented patients

Traditional NeurolepticsThioridazine (Mellenil) 10-800 mgPenphenazine (Tailafon) 2-66 mgHaloperidol (Haldol) 0 .540 mg

Buspirone Shown to be effective occasionally for nocturnal agitation inClonidine 0.1-1.2 mg Opiate withdrawal insomnia, refractory posttraumatic stressValerian

Others5 4 0 mg

elderly patientsdisorder, and treatment-resistant bipolar disorderand no comparisons to other drugs

400-900 mg Limited evidence of mild hypnotic effect; little safety data

21. Which agents should ot be prescribedfor sleep?Ethchlorvynol, methaqualone, and barbiturates no longer have a place as sedative/hypnotic

agents alone. They have greater risk of abuse, dependence, and lethal overdose and tend to lose ef-fectiveness much more rapidly than benzodiazepines. Alcohol is sedating but promotes nocturnalawakenings, and severely impairs sleep quality; tolerance develops rapidly. Chloral hydrate is nowfelt to be of only brief, limited usefulness because of overdose potential, rapid tolerance, GI distur-bance, and interactions with other drugs. A review of all evidence about melatonins efficacy foundno evidence that it improves sleep. There are also concerns that melatonin may inhibit ovarian func-tion, alter immune system, or cause vasoconstriction of cerebral and coronary arteries. Patientstaking steroids, those with an immune disease, cancers of the immune system, and women of child-bearing age should be counseled not to use it.22. Are sedative-hypnoticsassociated with homicidal behavior psychotic reactions or agita-tion?

Short-acting hypnotics have been associated with agitated states, sleepwalking, psychotic reac-tions, and at least two cases of homicide. Triazolam has been associated with at least two cases ofhomicide. It is suspected that the underlying pathology that caused the insomnia may have been amajor factor. A committee of the U.S. Institute of Medicine thoroughly reviewed all studies and liter-ature related to triazolam and concluded they do not support clearly the existence of a uniqueprofile or syndrome of adverse events. Zolpidem has been associated with sleepwalking andpyschotic reactions that are unrecallable the next day. With the million of users of these drngs, it is un-likely that they represent a significant hazard. It is prudent to avoid short-acting sedatives in patients


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278 The Use of Stimulants i n Psychiatric Practicewith history of severe agitation, highly anxious states, and impulsiveness and to keep sedative hyp-notic dosages within accepted parameters.

BIBLIOGRAPHY1. Bunney W E Jr, Azarnoff DL, et al: Report of the Institute of M edicine Co mm ittee on the Efficacy and Safety2. Greenblatt DI, Harmatz JS von Moltke LL, et al: Comparative kinetics and dyn am ics of zaleplon, zolpidem,3. Kryger M, Roth T. Dement W D (e ds): Principles and Practice of Slee p Medicine, 3rd ed . Philadelphia, W.B.4. Lob0 BL, Gree ne W L: Zolpidem: Distinct from triazolam? Ann Pharm acoth er 31(5):625-632, 1997.5 . Mendelson W B: E fficacy of melatonin as a hypnotic agent. J Biol Rhythms 12(6):651-656, 1997.6. National Institute of Mental Health, National Institutes of Health: Drugs and Insom nia. ConsensusDevelopment Conference Summary, vol4 , no 10 Bethesda, MD , U S . Department of Health and HumanServices, 1984.7. Nolen TM : Sedative effects of antihistam ines: Safety, perform ance , learning, and quality of life. Clin Ther

19(1):39-55, 1997.8. Poceta JS, Mitler MM: Sleep Disorders: Diagnosis and Treatm ent. Totowa, NJ Hum ana Press, 1998.9. Reite M L , Nagel KE, Ruddy JR : C oncise Guide to the Evaluation and M anagement of Sleep Disorders.10. Wagner J Wagner ML, Hening WA: Beyond benzodiazepines: Alternative pharmacologic agents for the

of Halcion. Arch Gen Psychiatry 56:349-352, 1999.and placebo. Clin Pha-maco l Ther 64(5):553-561, 1998.Saunders, 1999.

Washington, DC, American P sychia tric Press, 1997.treatment of insomnia. Ann Pharmacother 32(6):680-691, 1998.

52. THE USE OF STIMULANTS INPSYCHIATRIC PRACTICE

Hubert H h o ~ l a s o ~ ,u . M . D .

1. List the common stimulants prescribed in psychiatric practice.Generic Name Trade Name Dose RangeDextroamphetamine Dexedrine; Dextrostat 5 60 mg/dayDextroamphetamine amphetamine Adderall 5 60 mg/dayMethy lphenidate Ritalin; Ritalin SR; 5 60 mg/dayModafinil Provigil 100400 mg/day

(mixture)Metadate; Metadate ER

2. Describe the physiologic effects of stimulants.Stimulants increase catecholaminergic activity in the brain through inhibition of monoamineoxidase (MAO), blockade of neuronal catecholamine reuptake, and direct release of catecholaminefrom nerve terminals. Serotonin (5HT) activity at the neuronal level also i s altered. The resultantphysiologic state is characterized on electroencephalography (EEG) by increased power, especiallyin the alpha range. This finding is related to the clinical state of arousal associated with the use ofstimulants. Patients taking stimulants typically report activation, increased motivation, improvedmood, and even euphoria (which may be followed by a dysphoric crash when catecholamine storesare depleted in the brain), suppression of drowsiness, and decreased need for sleep. Blood pressureand heart rate may be increased, and appetite suppression is common.Among the unpleasant physiologic effects of stimulants are increased sweating, restlessness andagitation, and stereotypic movements such as teeth grinding, jaw-clenching, and skin picking.Sexual functioning may be impaired, with decreased libido in both men and women, inability tomaintain an erection in men, and anorgasmia in women.

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51. Sedative-Hypnotic Drugs