J Am Board Fam Pract: first published as 10.3122/jabfm.8.5.400 on 1 September 1995. Downloaded from Serotonin Syndrome In Parkinson Disease ni{/l[(' M. Wc>iss, Mn
Parkinson disease is a progressively debilitating cent, white cell count 14,500 I11llll with 7H per disease of the extrapyramidal motor system. cent segmented ncutrophils, 17 pcrcent lympho Components of dementia, as well as depression, cytes, no band cells, and a platelet count of have been recently rccognized as part of the syn 276X 103/111111'. Urinalysis was unremarkable as drome. As psychopharmacology bccomcs more were results of a urine toxicology screening test. advanced in the treatment of clusters of symptoms, His ammonia level was 330 mg/dL. new pitfalls arise. The "serotonin syndrome" is a An electrocardiogram showed sinus tachycar complic1tion of the use of monoamine oxidase dia, and findings on a chest radiograph were inhibitors (MAOls) and selective serotonin re within normal limits. Computed tOlllography uptake inhibitors (SSRls). The former are used as (CT) of his head showed cvidcnce of a right sub anti parkinson drugs, ,lS well as antidepressants, occipital craniotomy but no mass, midline shift, and includc phenelzine (Nardil), tranylc}11romine infarct, or hemorrhage. Findings from a lumbar (Parnate), and selegiline (Eldepryl). The latter puncture were unremarkable. make up the newer genen1tion of antidepressants, Meanwhile, further history was obtained from such as fluoxetine (Prozac), paroxetine (Paxil), and the patient's f~lIni!y, who said that the patient had sertraline (Zoloft). A casc is presented that serves had Parkinson disease for 16 years. Carbidopa to illustrate the drug interactions and review the levodopa (Sinemet) therapy began 3 years after syndrome. the disease onset, and the medication improved A 50-year-old man was found outside a nearby his symptoms substantially. He denied any history f{)od outlet in a state of agitation with generalized of encephalitis or drug use. His surgical history spasms. Paramedics wcre called, and the patient was noteworthy for removal of a right cerebellar was brought to the emergcncy department. arteriovenous malformation that was incidentally On arrival, his temperature was )(17°F rectally, discovered on CT of his head, which was per blood pressure 1971119 I11ml Ig, heart ratc 12 H/min, formed for evaluation of the Parkinson disease 10 and rcspiratory rate 40/min. The patient was in years prior to admission. coherent and had seizure-like muscle trcmors of He was taking large doses of carhidopa-Ievo
both upper and lower extremities. Neurologic dopa, 251250 four times a day, and a sustained http://www.jabfm.org/ examination was notable for rapid, dyskinetic release form (Sinemet CR), 501200 two tahlets movements mainly in the hands and feet bilater each day. In addition, he was taking selegiline, ally. I Ie had moderate rigidity in both upper and 10 mg/cl. The patient had been prescribed sertra lower cxtremities, his deep tendon reflexcs were line, 50 mg/d, for depression 2 weeks prior to ad 2 + bilaterally, and his toes were downgoing. mission. He had been forced to retire from his job Laboratory data wcre as follows: sodium 155 as a chemical engineer at the California Institute mEq/L, potassiulll 5.0 mEq/L, chloride 113 mEq/L, of 'Ilxhnology because of his Parkinson disease on 4 October 2021 by guest. Protected copyright. bicarbonate 24 mEq/L, blood urea nitrogen 21 and had become despondent ahout his physical mg/dL, creatinine I.H mg/dL, glucose 94 mg/dL. detcrioration. He had no recent history of expo The creatininc kinase was 1029 U/L, with an MB sure to ,1Il inhalationa] anesthetic or a neuroleptic fraction of 6.5 U/mL, and index 0.6 pcrcent. The medication. hcmoglobin was I.~.H g/dL, hematocrit 40 per- The patient was thought to have the neuro leptic malignant syndrome despite no history of antipsychotic medication ingestion. He was ad Sui>lllitted, revised, 12 :\by I (!'!5. mitted to thc intensive care unit for further obser Frolll the Dcpartillent of Faillily ,\ledicine, Kaiser I'enna vation. Levodopa, bromocriptine, and supportive nente ,\lediC:11 Center, Fontana, California. Address reprint therapies were administered, and he improvcd rC'lIll'sts to l)i:lIle ,\1. \\'eiss, :\11), Departillent of Faillily ;\ledi cine, Kaiser l'erlllanente :\1edical Center, ()<)() I Sierra Avenne, overnight. The selegiline and sertraline were dis FonLl1la, CA ()]l.l5. continued. Thirty-six hours after admission he
4-00 JABFP Sept.~(kt. 1t)95 Vol. H No.5 J Am Board Fam Pract: first published as 10.3122/jabfm.8.5.400 on 1 September 1995. Downloaded from was transferred from the intensive care unit to a Some drawbacks observed with selegiline are ward bed, never requiring intubation. He did suf that it irreversibly inhibits MAO-B, it tends to be fer from a component of rhabdomyolysis with nonselective for MAO-B at higher doses (thereby subsequent renal insufficiency. Total creatinine creating risk for the "tyramine cheese" effect), kinase reached a peak of 30,000 UIL. Renal func and it has somewhat weak amphetamine metabo tion returned to normal with hydration and alka lites. Newer drugs are being actively investigated linization of the urine. Two and one-half days to overcome these problems,f' after admission, the patient was released in stable condition. All blood, urine, and cerebrospinal The Serotonin Syndrome fluid cultures remained negative. Clinical depression is now recognized as occur ring in nearly 50 percent of patients with Parkin Discussion son disease. To treat these patients fully, anti Parkinson DtsellSe depressants are being prescribed in ever-growing Paralysis agitans, or Parkinson disease, was first numbers. Clinicians are becoming increasingly described in 1817.1 Occurring sporadically in the familiar with the third-generation antidepressants general population, it is a progressive, debilitating as a result of their circumscribed side-effect pro disorder with its first onset in mid to late life. De file/ and it is common to find patients on fluoxe spite extended research the cause is not well un tine and sertraline as opposed to the older tricy derstood. Two related conditions resulting in simi clic antidepressants. lar symptoms are postencephalitis parkinsonism As a result a new syndrome known as the sero and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyri tonin syndrome has come to be recognized.8- 16 1t dine (MPTP) intoxication (a drug of abuse) pro results from a combination of MAOIs with selec viding evidence for an environmental insult. tive serotonin reuptake inhibitors (SSRIs), such as L-tryptophan, clomipramine, fluoxetine, and Clinical Syndrome sertraline. Clinically, the serotonin syndrome is Symptoms of the full-blown syndrome are unmis similar to the neuroleptic malignant syndrome takable - stooped posture; stiff, slow move that occurs when antipsychotic medications are ments; impassive facies; and rhythmic tremor at combined with dopamine receptor blockers.17 rest. Symptoms generally begin asymmetrically Signs and symptoms include the acute onset of and progress to symmetric involvement. There is fever, confusion, myoclonus, hyperreflexia, dia no paralysis, but the progressive tremor and stiff phoresis, tremor, diarrhea, and incoordination. ness make activities of daily living nearly impossi Resolution is usually equally rapid, in contrast to http://www.jabfm.org/ ble in the end stages of disease. Deep tendon re the neuroleptic malignant syndrome, which can flexes, as well as sensory perception, remain take up to 1 to 2 weeks to resolve fully. intact. Nearly one-half of patients suffer from de The syndrome occurs in both sexes and in pressive symptoms. adults of all ages. There have been 38 cases reported during the past 12 years. The typical 'J'reatment scenario is one in which medications are being The mainstay of treatment has been to provide an altered for a variety of reasons - efficacy, side on 4 October 2021 by guest. Protected copyright. exogenous source of dopamine. The timing of effects - and an overlap between the serotonin this intervention is critical, because dopamine re reuptake inhibitors and the MAOIs causes hyper placement is not without side effects, including stimulation of brain-stem and spinal-cord seroto precipitation of dyskinesias, the on-off phenome nin receptors. It is now recommended that a full non (sudden variation in response), mental confu 5 weeks lapse after discontinuing fluoxetine and sion, and loss of efficacy. before starting MAOI treatment. More recently, the selective monoamine oxi In the case described, a selective MAO-B in dase B (MAO-B) inhibitor selegiline2 has been hibitor was taken with sertraline. Although found to delay by 1 year the need for levodopa ther MAO-A rather than MAO-B is specific for sero apy.3,4 The most intriguing hypothesized mode of tonin metabolism, there have been reports impli action is the inhibited production of free radicals cating MAO-B inhibition in a nonspecific reac ·, 5 that cause lipid membrane degra danon m neurons. tion with serotonin reuptake inhibitors. It is
Serotonin Syndrome 401 J Am Board Fam Pract: first published as 10.3122/jabfm.8.5.400 on 1 September 1995. Downloaded from currently not advised to prescribe selegiline with 5. DAIATOP: a llIulticente,' controlled clinical trial in any of the selective serotonin reuptake inhibitors. early Parkinson's disease. Arch Neurol I I)se); Treatment consists of removing the offending 4(>:1 052 -60. 6. Fowler .IS, Volkow NU, Logan j, Schlyer Uj, agents and providing supportive therapy. Active MacGregor RR, Wang (;.1, et al. MOlloallline oxi serotonin ant
402 JABFP Sept.-Oct. 1(1)5 Vol. 8 No.5