http://exhibits.library.stonybrook.edu/mfp/files/original/f9143989b4f022343ed9672f34b2d359.pdf 1500dfbcc8282737a3c8c3677182eaf9 PDF Text Text WITHDRAWAL SYMPTOMS FOLLOWING DISCONTINUATION 1 OF IMIPBAMINE THERAPY JOHN C. KRAMER, M.D.,2 DONALD F. KLEIN, M.D.,3 AND MAX FINK, M.D.‘ [Reprinted from THE AMERICAN JOURNAL OF PSYCHIATRY, V0]. 118, No. 6, December, 1961] �, . 0 i ~ I I‘NG- DISCONTIN'UATION OFIMIPRAMINE THERAPY 1 . V IOHN _'.-KHAMEH, M.D;,2 c: DONALD “E KLE‘I‘NQMD.) mMAXFIN‘K, Mgn.4 r v I ' �1961 1 CLINICAL NOTES 549 WITHDRAWAL SYMPTOMS FOLLOWING DISCONTINUATION 1 OF IMIPRAMINE THERAPY JOHN C. KRAMER, M.D.,2 DONALD F. KLEIN, M.D.,3 AND MAX FINK, M.D.4 On discontinuation of imipramine 5 treatment some psychiatric patients reported nausea, vomiting, dizziness, coryza, muscuAided, in part, by grant MY—2715 of National Institute of Mental Health, National Institutes of Health, USPHS. 2 Post Doctoral Research Fellow, USPHS, 19601 1961. Mental Health Career Investigator, USPHS. From the Department of Experimental Psychiatry, Hillside Hospital, Glen Oaks, L. I., N. Y. 5 The cooperation and assistance of Ceigy Pharmaceuticals is gratefully acknowledged. 3 4 lar pains and malaise. The symptoms were first regarded as conversion phenomena, but after several repetitions were considered due to physiological withdrawal. Of the patients treated with imipramine 45 had been observed within the hospital during withdrawal of medication. Treatment was instituted with oral doses of 75 mg. daily and usually increased each week in 75 mg. steps. The daily maintenance dose was 300 mg./day in 34 patients, more than 300 mg./day in 3 patients, and less than �550 CLINICAL NOTES 300 mg./day in 8 patients. We reviewed our interview records and the daily nursing notes, noting reports of withdrawal symptoms within 48 hours of cessation of medication in 25 of the 45 patients. Most prominent were nausea with or without vomiting—16 subjects, headache— 10, giddiness—lO, coryza—8, chills—6, weakness and fatigue—5, and musculoskeletal pain—4. Twenty—two of 26 patients treated for 2 months or longer reported withdrawal symptoms, while only 3 of 19 patients treated less than 2 months reported similar symptoms (p< .001). The 25 patients who had been treated for more than 2 months were rated for severity of symptomatology. The reaction was scored as “marked” if subjects reported more than 2 different symptoms with significant distress and as “minimal” if they reported fewer than 2 symptoms causing minor distress, or no symptoms. Of 13 patients with a medication tapering and termination period of less than 2 weeks, 8 had marked withdrawal symptoms and 5 mini— mal. Of 12 with a medication termination period longer than 2 weeks, only 2 subjects demonstrated marked withdrawal symptoms (p:.05). These results are in keeping with the general experience that the intensity of physiological withdrawal symptoms is directly proportional to the duration of drug administration and the abruptness of withdrawal. We could not relate the withdrawal syndrome to the size of the maintenance dose, since our range was too small. However, our modal schedule of 300 mg. per day is larger than the usual clinical schedule of 100 to 150 mg. per day and may account for the inconspicuousness of this phenomenon in other studies. We observed that allowing a period of 2-4 weeks for withdrawal was prophylactically effective. When symptoms on imipramine discontinuation occurred they could readily be treated by resuming imipramine at 50 mg. daily and gradually decreasing over a 1-week period. [ December DISCUSSION A physiological withdrawal syndrome following the termination of treatment with opiates, demerol, barbiturates, glutethimide, alcohol, chlorpromazine and meprobamate is well known. Recently withdrawal symptoms with methaminodiazepoxide(2), nialamide(1) and alpha-ethyltryptamine(5) have been reported. Kuhn( 3) and Mann and Macpherson(4) have also reported symptoms on abrupt imipramine withdrawa1. Until recently the physiological withdrawal syndrome was considered restricted to CNS “depressants” such as opiates, barbiturates and alcohol. This was confirmed by the absence of such a syndrome with “stimulant” drugs such as cocaine, d-amphetamine, marijuana, mescaline and LSD. The occurrence of such a syndrome with imipramine, nialamide, and alpha-ethyltryptamine is of considerable interest, therefore, since these drugs have been loosely referred to as “psychic energizers” with energetic effects similar to “stimulant” drugs. It is apparent that a simple depression—stimulation dimension is inadequate to describe the complexity of drug effect both physiologically and behaviorally. The withdrawal syndrome complicates the evaluation of patients after drug discontinuation since both patients and physicians often interpret the onset of symptoms as an upsurge of “anxiety” related to incipient relapse, and resume treatment with the gratifying subsidence of the “anxiety.” This may cause both patients and physicians to overvalue the importance of the medication to the patient’s stability. BIBLIOGRAPHY 1. Hollister, L. E., Motzenbecker, F. P., and Prusmack, J. J. : J. Clin. Exp. Psychopath., 21 : 212, 1960. 2. Hollister, L. E., Motzenbecker, F. P., and Degan, R. 0.: Psychopharmacologia, 2: 63, 1961. 3. Kuhn, R: Schweizerische Medizinische Wochenschrift, 87: 1135, 1957. 4. Mann, A., and Macpherson, A. : Canad. Psychiat. Assoc. J., 4: 38, 1959. 5. Turner, W. I., and Merlis, S. : J. Neuropsychiat., 2 : 1961. ��Htth¢r¢wnl Symptonu ralluvtnz Discontinuation at In1pran1uo fhurtpy {can 6. {rt-st, H.D.#, nonald and r. Kissn, x.n.u‘ In: link, 3.9. from tho Departnont of Exporincntal rayohigtry, 3:110:40 lalpltal, Olen 00kt, 5.1., [.1. floatorll Raconrch fallow, 88,38, 1960~1961. oqnontnl lunlth euro-r Iavuatagutor, ssrus. Aided, in part, by grant l1~2715 or Intionul Institute 01 Hantnl Health, Int1¢n¢1 Iu|t1tutoa at laulth, yarns. the caoportttou and aauiutanoo ot_6.1¢y Pharancauttcal: O P98? 52.301111: nekuuvlcdaod. VI: 6/29/61 13 �discontinuation of iliprsniss trsstnsnt sons pstissts, ands: obssrvssisa ts: s vsristy a: psychistric sysdrssss, rsportsd nsssss, vssiting, dissinsss, ssryss, ssscslsr psins sad Islsiss. Ens sysptsss ssrs first rsgsrdsd ss osmvsrsisa phsnousns, but stisr ssvsrsl rspstitisns vs sonsidsrsd thsss to be dss to physiological withdrsssl sad an sttolpt vss nsds to dotsrsins their trsqusaoy sad varisty. o: the pstisats trsstsd with isiprssins during sn sightoon nsnth psriod, forty-11's hsd bssn observed within the hospitsl sstting during withdrawal of ssdissties. In thsss subsects trsstnsnt was instituted with arsi dosss st 75 s; dsiiy sad ssnsliy issrssssd sssh sssk in 75 as stsps. Ins dsiiy‘ssistsnsaes dsss ass zoo aglsay in thirty-tour puss-ntsg loss than 300 ltldly in tires pstisass; and loss thin 300 Is/dsy in sight 0n pstisats. rsvisssd our intsrviss rssords and fits dsily ssrsiac notss, noting rspsrss o: uithdrsssl symptoms within k8 hours of ssssstisa or sodiostion in 25 of tho h! pstisnts. (rsbls I) Vs n“.-.IABLE I -D.-”- �2.510 I aynptonl Within an Intro 01 cunna$1on or Iniprnnino therapy’ Pnttontl conning theft?! Patients reporting Iynptonu hS 25 azggtons l:unou (and/or vomiting) 16 Houdnoho 10 GiddinOII . 10 Darya: chill: taintnuuu HIIoqu-Ikolotsl pain Hoaknosu or rmma �.29 ovidoat whoa tho aurorolottonohip otguitioont ttoo o: trootlont and tho oppooroaoo of orlptono oro oomporod. (Toblo I!) toasty-too of tvonty-otx patients trootod for two ooutho or longor roportod withdruvol oyuptono, whilo only throo of ntnotoon potionto trootod loo: than too nontho roportod otnilor oynptono. 1o A II O .‘O--.. fAILB to dotornino tho rolotion of tho obouptaooo ot nodiootton withdrovol to indoood oyuptouo, tho twentyrtvovpottonto who bod boon trootod for noro thou two ooutho ooro rotod to: oovortty o: oynptoootoloay. rho rooottoo woo ooorod oo 'norkod' 1: lobaooto roportod ooro thou two dittoroot oynptono with otgaitioont diotrooo and to "minimal“ at tho: roportod towor than two oyoptono oonoins lino: atotrooo, or no symptolo. Too groupo ooro doriaod according to otothor tho poriod or Iod1oot1on rodootton woo looo thou too rook: or too uooko t or longoo. (foblo III) “-Qfl‘..-. TABLS III �Ink}: 1! nurution of Iniprnltno Therapy w1%hdr¢vn1 Symptoms It Withdrawal Symptonu (lubaootl) (subjects) in. isn‘t. I 16 fun South: or hangar 22 h Lon. thin x9 .- 23.91. P < .001 2gblo £51 rurtod or 3:3: Gestation In Patients rruatcd st Lcnlt fro abnthn Withdrawal 8232t¢nl lurked . Lon. than rug minimal VIDEO 6 5 fun with: or Long.» a 10 p ~ .05 (Fisher) (h) �~3- !haaa raaalta art in kaaping vita fiha can-val asparianaa ihat tho iataaaity a: phyaiolocical withdrawal aylptoua is directly proportional in tho duration at drug adaiaiatration and tha abruptaaaa at vifihdraaal. Va scald not ralata tha appaaranaa of at: withdrawal ayndroao to tho aiaa o: tho aaiatauanea doaa, ainoa our ranaa uaa too shall. flovavar. our natal aahadala a! 300 I; ha: day in largo: than tho aaaal clinical aahadala a: 100 ta 150 a. par day and nay account for an. inaauapioaaaaaaaa a: thin phaaaaaaaa in Qatar atadiaa. It Iaat ha aataa that withdrawal aylpiaaa was. unvaried by aaa patiaat aha III traataa la: tua lantha at 75 In; par «7. a marina. daaa at abaarvad that alluviag a parted at 3-h wacktar withdrawal ran prayhylaatiaally attaetiva. ihan ayaptaaa an iaipraaiaa diaeoatinaatiaa acaurrad they coal! readily be treated by raaaaing iaipraaiaa at Ha , 56 a; daily aid gradually aaaraaains era: a parted. one tack �9h. accurrcauc a: a vhf-1010:1931 utthdrnnal lyndronc tollcrtlg the tor-tnutton o: troninoat with optntcl, duu.rol, burhtiurltcn. all$othilado and 1100301 1! wall kntln¢ looantly withdrlvul Irlgten- attachlsrptonnsaao (2), Isthnatnodinuapcxtlo {1). nialnuldo (5}, alpha-oihyittyp‘anlno (9) and nuptniiluto (1,3,6) lav. icon rcporfiod. tan: (8) ha; ciao obstrvod lyuyton‘ on abrupt znlprnltno withdraanlo Until riotatly it. phytiologteal iithdruu:1 cyadrono was coalidtroi routrtetcd to 618 'dcpréunsatn' Inch OI splat... barblfiurnsos and alcohol. this was contirnod 57 Sh. tbacnco of such a cyndruno with “stannlsnt‘ drugs tank .3 cocgtno, d-tlphotanino, unhealino and £39. In. accurronoc at such antisulan, a syndrcnn with tulprlltnu,43131anldn, and alpha.ihrltryptaazno 1- or etalldnrahll Satori-t, ‘horutorc. can-o thus. drug: havn baa: 1.90.17 rtrorrcd to a: 'payuhao 0303:1302.“ 11$) unaruo‘tc o£1¢ctn 01-11:: ' human an to u .1»:am... It 1.- .pnmt Canto-liaa-stxlnlatioa dincnulun 1: tnnlcquat. to donoribu tho.¢olploxtty or drug effect hath phyuso« logically and behaviorully. in. at withdrawal 9:362:30 conpl1oatbn tho avnlunttou pcttcutn utter drug dicooutsnuatton, both oltniually . �hoth and patina“ an” maximum, punch:um 1“.»er tn ant a mu», (mans, to. u a: spur" a: ‘uuaotyfl "1am to menu“ "up“. and hum a mum ”amt an m ”any“. «bum» a: a. 'mtoty'. m. any at!" ”a and plantain: to ova-van tho moral» of a. plum“ noun“... to tho grunt“ gummy. and �m 1. no taunts-u at «1pm» ”um“ product. phyutoIocto-l withdruwnl uynptonu, which arc rolutod to luasth of ‘rontnaut and abruptuocn o: withdrivui. aylptonn may also be rolntad to douaco luv-1o I. H1thdrar¢1 lyyptons any h. militia-d qr oltntuutod by running fitchuaquol. I it. aneurraaac of : withdranul syndrong lath tnlprgnluo to porttnoafi ta tn. coucoptunltus$1.: or its paynhowhnrnaaolocical notiviflr, and to 3. prabltna I: clinical Isaac-hunt. �1. mu, 3.1., at. an... Ida W. ’- 33.3,. 1. 1023, 1955. Inch. 3-.» 9.3.: Mac, 3.3. and 833. 1958. lulu, 1.3.: m: a, J, 931. 1959. 'mnfi: MI 801301, id. 8.. vgumMe autumn, m ncfirtI-ltll, It! tort, 1956, 96. 5. lanai", In!” ”summer”, hr. and Pam-suck, 3.3.: 3 lmhflnfih, 3;: 212, 1960. g, nun: L“ 6- lolltltor, L.R. and fllcsanar, !.8.s £3!3§22§£££££2¥3‘§2& 196°. 3”, ;. 7. amour, In!” Runabout», LP. and Baa, the” It. ”that, BA” in W a W. I. ma. M 2- ‘3: 1951. 1135, 1957. 9. Mar, m1. ad lit-r110, 373, 1961 (app)... 1) 8.1 J, Inn-3mg; . g: 9.1: � Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Published Works Text A resource consisting primarily of words for reading. Examples include books, letters, dissertations, poems, newspapers, articles, archives of mailing lists. Note that facsimiles or images of texts are still of the genre Text. Dublin Core The Dublin Core metadata element set is common to all Omeka records, including items, files, and collections. For more information see, http://dublincore.org/documents/dces/. Title A name given to the resource Withdrawal symptoms following discontinuation of Imipramine therapy. Amer J Psychiat, 118:549-50. Type The nature or genre of the resource Text Identifier An unambiguous reference to the resource within a given context mfp-02-01-003-56-022 Date A point or period of time associated with an event in the lifecycle of the resource 1961 Creator An entity primarily responsible for making the resource Kramer, John C.; Klein, Donald F.; <a title="Fink, Max, 1923-" href="http://id.loc.gov/authorities/names/n79039548" target="_blank">Fink, Max, 1923-</a> Subject The topic of the resource Published Works -- Articles and Reviews Relation A related resource The Max Fink Collection Description An account of the resource Reprint (Clinical notes) and [preprint]. Reprint from THE AMERICAN JOURNAL OF PSYCHIATRY, V0L. 118, No. 6, December, 1961 Rights Information about rights held in and over the resource <a title="IN COPYRIGHT - EDUCATIONAL USE PERMITTED" href="http://rightsstatements.org/vocab/InC-EDU/1.0/" target="_blank">IN COPYRIGHT - EDUCATIONAL USE PERMITTED</a> Source A related resource from which the described resource is derived Special Collections and University Archives, University Libraries. Stony Brook University Libraries (State University of New York). Language A language of the resource en-US Format The file format, physical medium, or dimensions of the resource application/pdf Publisher An entity responsible for making the resource available Contributor An entity responsible for making contributions to the resource Published