52. the use of stimulants in psychiatric practice

8/12/2019 52. the Use of Stimulants in Psychiatric Practice

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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 eds): 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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The Use o stimulants in Psychiatric Practice 2 93. Wh at are the comm on uses of stimulants in psychiatric practice?The most com mon use of stim ulants in psychiatric practice is in the treatment of attentiondeficithyperactivity disorder ADH D) in children and occasionally adults. AD HD is comm on inchildren, but rare in adults). Th e Food and Drug Administration FDA) sanctions the use of stimu-lants in this disorder.Also approved by the FDA is the use of stimulants to treat narcolepsy a rare disorder in whichthe suffe rer is plagued by sleep attacks. Modafinil is specifically approved for narcolepsy.Impo rtant uses of stimulants beyond those approved by the FDA center on the treatment ofmood d isorders and amo tivational states.Stimulants m ay be added to a partially effective antidepressant regimen to augm ent the anti-depressant action see Chap ters 47 and 49) when it is impractical to increase the antidepressant dose,either because of adverse effects or because the maximal dose already has been reached w ithout suf-ficient improvement.Amo tivational states which may or may not be tied to depression) may respond acutely to theuse of stimulants. Such states include medically compromised p atients who are not participating

actively in treatment and therefore are at risk of further deterioration of functioning. The typical sce-nario involves elderly persons, persons who are having difficulty with weaning from a ventilator, pa-tients infected with the human imm unodeficiency virus HIV), poststroke victims or postoperativeneurosurgical patients, and terminally ill patients. Behavioral control and cognition have improvedwith stimulant treatment in chronic closed-head-injury patients.Clinical Pearl Using a stimulant 5 mg of dextroamphetamine) helps to d ifferentiate betweendepressed and dem ented patients. Depressed patients are likely to respond with improved m ood,cog nition, and alertness, wh ereas demented patients may show increased alertness but worsenedcognition.

4. Wh at are inappropriate uses of stimulants?Stimulants are not effective as the primary treatment for depression. Additionally, stimulantsshould not be used to relieve normal fa tigue states. In general, weight contro l and appe tite sup-pression are not clinically app ropr iate uses for stimu lants becau se of lack of efficacy over timeand risk of adv erse effects. B ehaviorally based treatments are better than stim ulants for weightcontrol.5. List and discuss some of the comm on problems associated with prescription of stimulants.Tolerance. The sympathomim etic effects of stimulants diminish quickly at a steady dose. Thuspersons using stimulants to produce euphoria, appetite suppression, energy, and w akefulness become

quickly disappointed and seek to increase the dose to achieve the former level of stim ulation. Of i n -terest, tolerance does no t develop to the therapeutic benefit of stimulants in ADH D, or to their anti-depressant effects when used to augment treatment of depression, or in medically ill patientsmaintained on stimulants for amotivational states.Abuse. Stimulants have been extensively abused i n the past because they are known to produceeuphoria, energy, and wakefulness. An historically important form of stimulant abuse occurredduring World War 11 Allied and Axis fo rces used amph etamine extensively. Japanese fighter pilots,on suicide missions in the Pacific, used amphetamine. Postwar Japan experienced an epidemic ofamphetamine abuse when large stockpiles of amp hetam ine from the military w ere placed on theopen mark et. Th e potential for abuse has caused stimu lants to becom e heavily regulated in theUnited States.Adverse effects. Com mon or important stimulant-induced side effects include:AnxietyImtability PalpitationsInsomniaDysphoria teeth grindingljaw clenching)Emotional labilityDecreased appetite Paranoia

Increased heart rate and blood pressureTics and o ther involuntary movem entsTransient growth suppression in children


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280 The Use of St imulan t s in Psychiatric PracticePsychological dependence HallucinationsPhysical dependence PsychosisExacerbation of other illnesses such as glaucoma, hypertension, anxiety disorders,Drug drug interactions.Stimulants may decrease metabolism and thus increase plasma level)Tricyclic/tetracyclic antidepressants PhenobarbitalWarfarin Coumadin) Phenytoin Dilantin)Primidone Mysoline) Phenylbutazone Butazolidin)Use stimulants with extreme caution in the presence of MA0 inhibitors because of the possi-bility of a hypertensive crisis. In addition, exercise extreme caution when prescribing stimulants topatients with bipolar affective disorder, as these compounds may induce mania or rapid-cycling.

psychotic disorders, and seizure disordersof certain drugs:

6. Summarize governmental regulationof stimulants.All stimulants except modafinil, which has a schedule IV designation) are classified by theU.S. Drug Enforcement Agency DEA) as schedule 11,along with certain narcotics. Additional regu-lations may vary from state to state, including the use of triplicate prescriptions for stimulants onecopy is filed with a state governmental agency). A proper state medical license and DEA certifica-tion are required for physicians to prescribe stimulants. Internationally there is much variability inthe regulation of stimulants. Sweden has banned stimulants, whereas they are available without pre-scription in other countries.7. Summarize practical information about prescribing stimulants.

Prescription o StimulantsDEXEDR INE RITALINMETADATE PROVIGIL ADDER ALL

How suppliedTablets)

PretreatmentevaluationConcurrentmonitoringStarting dose mg)AdultsChildrenIncrease doseweekly byDaily schedule

Maximal recom-mended dose

5 , 10mgOral suspension:

5 mglmlSustained release: 5,10, and 15mg

Cardiac, liver, andrenal functionNone

2-5- 102-5 3-5 yrs)5 6 yrs and older)5 mgTwice daily divideddose except in

sustained releaseform once daily)60 mg

10 and 20 mg 100,200 mg 5 , 10, 20, and30 mg

Cardiac, liver, and Cardiac, liver, and Cardiac, liver, andrenal function renal function renal functionNone None None

5-10 100-200 mg 5-105 No data in chil- 5dren under 165-10 mg 100 mg 5-10Two to three times Once daily in AMdaily except times daily

longer actingform once ortwice daily)

Twice or three

60 mg 400 mg 60 mgThere is no indication for the use of stimulants during pregnancy. Dextroamphetamine Dexedrine) andmethylphenidate Ritalin) pass into breast milk.


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282 Understanding Medication Interactions11. Pickett P, Masand P, Murray GB: Psychostimulant treatment of geriatric depression disorders secondary to12. SpencerT, et al: Pharmacotherapy of attention-deficit hyperactivity disorder across the life cycle. J Am Acad13. Woods SW, Tesar GE, Murray GB, Cassem NH: Psychostimulant treatment of depressive disorders sec-

medical illness. J Geriatr Psychiatry Neurol 3 3):146-151, 1990.Child Adolesc Psychiatry 35:409-432, 1996.ondary to medical illness. J Clin Psychiatry 47:12-15, 1986.

53 UN DERSTAN DING MEDICATIONINTERACTIONSDee Opp, R.Ph., BCPP nd Lyle Laird, Phccv~zD,BCPP

1. Why are drug interactions important to consider?To maximize therapeutic outcome and minimize adverse side effects, a prescriber needs to un-derstand how a drug works, how it is metabolized, and what side effects are common with the use ofthe medication. When you consider a new medication for use, you must know how it will interactboth dynamicallyand kinetically with other medications. For example, if a patient is currently onclonidine for hypertension, and a tricyclic antidepressant TCA) is being considered for therapy, theprescriber should know that the TCA could antagonize the alpha-2 agonist property of the clonidineand negate its antihypertensive effects. This is an example of a pharmacodynamic interaction. Thus,it is important to have an understanding of the mechanisms of action of medications to determine if

one is likely to antagonize or block the therapeutic effect of another.In many therapeutic regimens, physicians are faced with using more than one agent to treat orameliorate symptoms. All combinations need to be assessed for the presence of both kinetic and dynamic interactions.2. What are the mechanismsof psychotropic medication metabolism?Most of the psychotropic medications are metabolized by a process known as phase I metabo

lism. This type of metabolism is carried out hepatically by a group of enzymes known as the cy-tochrome P450 CYP450) mixed oxidase system. CYP450 enzymes break down the medicationsinto more water-soluble metabolites, which then are more easily excreted into the urine and elimi-nated from the body. In addition, phase I1 metabolism involves another group of enzymes in theliver. This system primarily results in glucuronidation of drugs, which also allows them to be ex-creted in the urine.A clinically important example is the interaction between the anticonvulsants, lamotrigine andvalproic acid. When these two medications are used together, valproic acid inhibits the phase 11process of glucuronidation, causing up to a 50 decrease in lamotrigines clearance and a signifi-cant increase in its half-life. This effect on the pharmacokinetic parameters of lamotrigine can in-crease blood levels and, hence, side effects most significantly, increasing the risk of Steven-Johnsons syndrome).3. Are there other ways medications interact beside via metabolism in the liver?Medications can interact through multiple mechanisms, and all concurrently. The difficult taskis to evaluate which one will influence the success of drug treatment the most. There are two maintypes of drug interactions: pharmacokineticand pharmacodynamic.Pharmacokinetic interactionsinvolve how one drug influences the normal movement of another drug in the body.For example, one medication may inhibit the absorptionof another. Ascorbic acid inhibits theabsorption of amphetamines and therefore decreases their effectiveness in the treatment of attentiondeficit hyperactivity disorder. Another type of interaction is how one medication may influence the

52. the use of stimulants in psychiatric practice

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