To review the published reports of neuroleptic malignant syndrome (NMS) associated with the use of selective serotonin-reuptake inhibitors (SSRIs) and second-generation antipsychotics.
Data Source:
Information was selected from a MEDLINE search of English-language literature (1950–May 2008). Manual search of all published cases indexed in MEDLINE (English language only) of NMS associated with second-generation antipsychotics was also performed.
Study Selection And Data Extraction:
Pertinent information from all reports obtained was included, with specific emphasis on patient age, sex, second-generation antipsychotic involved, SSRI or other antidepressant involved, time of onset of NMS symptoms in relation to medication changes, treatment administered, and outcome of the reaction.
Data Synthesis:
NMS has been reported with every second-generation antipsychotic agent. It is unclear whether concomitant therapy with other agents may increase the risk of NMS development via pharmacodynamic or pharmacokinetic mechanisms or both, The suggested pharmacodynamic mechanism for increased risk of NMS with concomitant use of SSRIs is the effect of serotonin on dopamine release. Serotonin further inhibits dopamine release and thereby may worsen a hypodopaminergic state induced by antipsychotics. Pharmacokinetic factors may also play a role in some NMS cases involving an SSRI by increasing antipsychotic concentrations. An examination of case reports seems to indícale that at least in some casos, a temporal relationship exists with the addition of an SSRI to existing antipsychotic therapy.
Conclusions:
The use of SSRIs may be associated with an increased risk of NMS development in (hose receiving second-generation antipsychotics. Clinicians should closely monitor patients for the potential development of NMS.
CaroffSN, MannSC. Neuroleptic malignant syndrome. Med Clin North Am1993;77:185–202.
2.
SusmanVL. Clinical management of neuroleptic malignant syndrome. Psychiatr Q2001;72:325–36.
3.
DuggalHS. Possible neuroleptic malignant syndrome associated with paliperidone. J Neuropsychiatry Clin Neurosci2007;19:477–8.
4.
HallR, ApplebyB, HallR.Atypical neuroleptic malignant syndrome presenting as fever of unknown origin in the elderly. South Med J2005;98:114–7.
5.
Diagnostic and statistical manual of mental disorders. 4th ed. (TR). Washington, DC: American Psychiatric Association, 2000.
6.
LevensonJL. Neuroleptic malignant syndrome. Am J Psychiatry1985;142:1137–45.
7.
PopeHG, KeckP, McElroySL. Frequency and presentation of neuroleptic malignant syndrome in a large psychiatric hospital. Am J Psychiatry1986;143:1227–33.
8.
NierenbergD, DischM, ManheimerE. Facilitating prompt diagnosis and treatment of the neuroleptic malignant syndrome. Clin Pharmacol Ther1991;50:580–6.
9.
GambassiG, CapursoS, TarsitaniP, LiperotiR, BernabeiR.Fatal neuroleptic malignant syndrome in a previously long-term user of clozapine following its reintroduction in combination with paroxetine. Aging Clin Exp Res2006;18:266–70.
10.
BhanushaliMJ, TuitePJ. The evaluation and management of patients with neuroleptic malignant syndrome. Neurol Clin2004;22:389–411.
11.
JaussM, KrackP, FranzM. Imaging of dopamine receptors with [123 I] iodobenzamide single-photon emission-computed tomography in neuroleptic malignant syndrome. Mov Disord1996;11:726–8.
12.
GrayNS. Ziprasidone-related neuroleptic malignant syndrome in a patient with Parkinson's disease: a diagnostic challenge. Hum Psychopharmacol Clin Exp2004;19:205–7.
13.
Choi-KainLW, PopeHG. “Atypical” neuroleptic malignant syndrome and the spectrum of malignant cerebrotoxic syndromes. Harv Rev Psychiatry2007;15:181–6.
14.
SpivakB, GonenN, MesterR, AverbuchE, AdlersbergS, WeizmanA.Neuroleptic malignant syndrome associated with abrupt withdrawal of anticholinergic agents. Int Clin Psychopharmacol1996;11:207–9.
15.
SpivakB, MalineDI, VeredY. Prospective evaluation of circulatory levels of catecholamines and serotonin in neuroleptic malignant syndrome. Acta Psychiatr Scand2000;102:226–30.
16.
NisijimaK, IshiguroT.Neuroleptic malignant syndrome: a study of CSF monoamine metabolism. Biol Psychiatry1990;27:280–8.
17.
PeloneroAL, LevensonJL, PandurangiAK. Neuroleptic malignant syndrome: a review. Psychiatr Serv1998;49:1163–72.
18.
NicholsonD, ChiuW.Neuroleptic malignant syndrome: a case study and review of the literature. Geriatrics2004;59:36–40.
FarverDK. Neuroleptic malignant syndrome induced by atypical antipsychotics. Expert Opin Drug Saf2003;2:21–35.
23.
ReulbachU, DutschC, BiermannT. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care2007;11:R4.
24.
PreskornSH. Neuroleptic malignant syndrome resulting from a complex drug-drug interaction: “I don't see “em.”J Psychiatr Pract2007;13:328–33.
25.
CaleyCF. Extrapyramidal reactions and the selective serotonin-reuptake inhibitors. Ann Pharmacother1997;31:1481–9.
26.
KatoD, KawanishiC, KishidaI. Effects of CYP2D6 polymorphisms on neuroleptic malignant syndrome. Pharmacogenetics2007;63:991–6.
27.
SpinaE, AvenosoA, FacciolaG, ScordoMG, AncioneM, MadiaA.Plasma concentrations of risperidone and 9-hydroxyrisperidone during combined treatment with paroxetine. Ther Drug Monit2001;23:223–7.
28.
SpinaE, D'arrigoC, MigliardiG. Plasma risperidone concentrations during combined treatment with sertraline. Ther Drug Monit2004;26:386–90.
29.
WetzelH, AnghelescuI, SzegediA. Pharmacokinetic interactions of clozapine with selective serotonin reuptake inhibitors: differential effects of fluvoxamine and paroxetine in a prospective study. J Clin Psychopharmacol1998;18:2–9.
AmesD, WirshingWC. Ecstasy, the serotonin syndrome, and neuroleptic malignant syndrome—a possible link?JAMA1993;269:869–70.
32.
AydinN, AnacE, CaykoyluA, AkcayF.Neuroleptic malignant syndrome due to citalopram overdose. Can J Psychiatry2000;45:941–2.
33.
BottlenderR, JagerM, HofschusterE, DobmeierP, MollerHJ. Neuroleptic malignant syndrome due to atypical neuroleptics: three episodes in one patient. Pharmacopsychiatry2002;35:119–21.
34.
CawrseN, WilsonS, WilliamsM, BurgeT.Neuroleptic malignant syndrome in burns patient. Burns2006;32:647–9.
35.
Del TaccaM, LattanziL, LastellaM. Genotype A1/A2 associated with neuroleptic malignant syndrome. Bipolar Disord2005;7:390–1.
36.
DuggalHS, KithasJ.Possible neuroleptic malignant syndrome with aripiprazole and fluoxetine. Am J Psychiatry2005;162:397–8.
37.
DursunSM, OlubokaOJ, DevarajanS, KutcherSP. High-dose vitamin E plus vitamin B6 treatment of risperidone-related neuroleptic malignant syndrome. J Psychopharmacol1998;12:220–1.
38.
FerioliV, ManesA, MelloniC, NanniS, BoncompagniG.Atypical neuroleptic malignant syndrome caused by clozapine and venlafaxine: early brief treatment with dantrolene. Can J Psychiatry2004;49:497–8.
39.
GarciaG, GhaniS, PovedaRA, DanskyBL. Neuroleptic malignant syndrome with antidepressant/antipsychotic drug combination (letter). Ann Pharmacother2001;35:784–5.
40.
GhaziuddinN, AlkhouriI, ChampineD, QuinlanP, FluentT, GhaziuddinM.ECT treatment of malignant catatonia/NMS in an adolescent: a useful lesson in delayed diagnosis and treatment. J ECT2002;18:95–8.
KasantikulD, KanchanatawanB.Neuroleptic malignant syndrome: a review and report of six cases. J Med Assoc Thai2006;89:2155–60.
43.
KaufmanKR, LevittMJ, SchiltzJF, SunderrramJ.Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis. Ann Clin Psychiatry2006;18:201–4.
44.
KernJL, CernekPK. Delayed risperidone-induced neuroleptic malignant syndrome (letter). Ann Pharmacother1996;30:300.
45.
KontaxakisV, Havaki-KontaxakiBJ, PappaDA, KatritsisDE, ChristodoulouGN. Neuroleptic malignant syndrome after addition of paroxetine to olanzapine. J Clin Psychopharmacol2003;23:671–2.
46.
LuT, ChuP, WuC, TsaiK, ChenW.Neuroleptic malignant syndrome after the use of venlafaxine in a patient with generalized anxiety disorder. J Formos Med Assoc2006;105:90–3.
47.
MatsumotoR, KitabayashiY, NakatomiY, TsuchidaH, FukuiK.Neuroleptic malignant syndrome induced by quetiapine and fluvoxamine (letter). Am J Psychiatry2005;162:812.
Nyfort-HansenK, AldermanCP. Possible neuroleptic malignant syndrome associated with olanzapine (letter). Ann Pharmacother2000;34:667. DOI 10.1345/aph.19239
PrécourtA, DunewiczM, GrégoireG, WilliamsonDR. Multiple complications and withdrawal syndrome associated with quetiapine/venlafaxine intoxication. Ann Pharmacother2005;39:153–6. Epub 2004 Nov 23. DOI 10.1345/aph.1E073
52.
ReddigS, MinnemaAM, TandonR.Neuroleptic malignant syndrome and clozapine. Ann Clin Psychiatry1993;5:25–7.
53.
ReevesRR, MackJE, TorresRA. Neuroleptic malignant syndrome during a change from haloperidol to risperidone. Ann Pharmacother2001;35:698–701. DOI 10.1345/aph.10137
54.
ReevesRR, MackJE, BeddingfieldJJ. Neurotoxic syndrome associated with risperidone and fluvoxamine. Ann Pharmacother2002;36:440–3. DOI 10.1345/aph.1A241
55.
RodriguezOP, DowellMS. A case report of neuroleptic malignant syndrome without fever in a patient given aripiprazole. J Okla State Med Assoc2006;99:435–8.
TaniiH, IchihashiK, InoueK, FujitaK, OkazakiY.Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam. Prog Neuro-Psychopharmacol Biol Psychiatry2006;30:1176–8.
58.
TarsyD.Risperidone and neuroleptic malignant syndrome (letter). JAMA1996;275:446.
59.
TsaiG, CrisostomoG, RosenblattML, SternTA. Neuroleptic malignant syndrome associated with clozapine treatment. Ann Clin Psychiatry1995;7:91–5.
60.
ZiegenbeinM, KroppS, HillemacherT, BleichS.Genetic predisposition to neuroleptic malignant syndrome in siblings (letter). Ann Pharmacother2006;40:574–5. Epub 14 Feb 2006. DOI 10.1345/aph.1G483
61.
TanakaE, HisawaS.Clinically significant pharmacokinetic drug interactions with psychoactive drugs: antidepressants and antipsychotics and the cytochrome P450 system. J Clin Pharm Ther1999;24:7–16.
62.
PriorTI, BakerGB. Interactions between the cytochrome P450 system and the second-generation antipsychotics. J Psychiatry Neurosci2003;28:99–112.
