Stahls Essential PsychopharmacologyPrescribersGuideWith the range of psychotropic drugs expanding and the usages of existing medications diversifying, we are pleased to present this very latest edition of what has become the indispensable formulary in psychopharmacology.This new edition features 16 added new drugs, including six fresh-to-market critical new compounds, and several older drugs for which there are proven and useful applications. In addition, many important new indications are covered for existing drugs, as are updates to the proles of the entire content and collection.With its easy-to-use, template-driven navigation system, the Prescribers Guide combines evidence-based data with clinically informed advice to support everyone prescribing in the eld of mental health.Stephen M. Stahl is Adjunct Professor of Psychiatry at the University of California, San Diego, and Honorary Visiting Senior Fellow in Psychiatry at the University of Cambridge, UK. He has conducted various research projects awarded by the National Institute of Mental Health, Veterans Affairs, and the pharmaceutical industry. Author of more than 500 articles and chapters, Dr Stahl is also the author of the bestseller Stahls Essential Psychopharmacology.FIFTH EDITIONStahls Essential PsychopharmacologyPrescribersGuideFIFTH EDITIONStephen M. StahlUniversity of California at San Diego,San Diego, CaliforniaEditorial assistantMeghan M. GradyWith illustrations byNancy Muntner675TRANYLCYPROMINETHERAPEUTICSBrands Farnatesee index for additional brand namesGeneric?Yes ClassMonoamine oxidase inhibitor (MA0) Commonly Prescribed for(bold for FDA approved) Major depressive episode without melancholiaTreatmentresistant deression Treatmentresistant anic disorder Treatmentresistant social anxiety disorder How the Drug Worksrreversibly blocks monoamine oxidase (MA0) lrom breakinq down noreinehrine, serotonin, and doamineThis resumably boosts noradrenerqic, serotonerqic, and doaminerqic neurotransmission

As the druq is structurally related to amhetamine, it may have some stimulantlike actions due to monoamine release and reutake inhibitionHow Long Until It WorksSome atients may exerience stimulant like actions early in dosinq0nset ol theraeutic actions usually not immediate, but olten delayed 2-4 weeksl it is not workinq within G-8 weeks, it may require a dosaqe increase or it may not work at allMay continue to work lor many years to revent relase ol symtomsIf It WorksThe qoal ol treatment is comlete remission ol current symtoms as well as revention ol luture relasesTreatment most olten reduces or even eliminates symtoms, but not a cure since symtoms can recur alter medicine stoedContinue treatment until all symtoms are qone (remission)0nce symtoms qone, continue treatinq lor 1 year lor the lrst eisode ol deressionFor second and subsequent eisodes ol deression, treatment may need to be indelniteuse in anxiety disorders may also need to be indelniteIf It Doesnt WorkMany atients have only a artial resonse where some symtoms are imroved but others ersist (esecially insomnia, latique, and roblems concentratinq)0ther atients may be nonresonders, sometimes called treatmentresistant or treatmentrelractorySome atients who have an initial resonse may relase even thouqh they continue treatment, sometimes called "ooout"Consider increasinq dose, switchinq to another aqent, or addinq an aroriate auqmentinq aqentConsider sychotheray Consider evaluation lor another diaqnosis or lor a comorbid condition (e.q., medical illness, substance abuse, etc.)Some atients may exerience aarent lack ol consistent ellcacy due to activation ol latent or underlyinq biolar disorder, and require antideressant discontinuation and a switch to a mood stabili/er Best Augmenting Combos for Partial Response or Treatment Resistance

Auqmentation ol MA0s has not been systematically studied, and this is somethinq lor the exert, to be done with caution and with carelul monitorinq

A stimulant such as damhetamine or methylhenidate (with caution, may activate biolar disorder and suicidal ideation, may elevate blood ressure)Lithium Moodstabili/inq anticonvulsants Atyical antisychotics (with secial caution lor those aqents with monoamine reutake blockinq roerties, such as /irasidone and /oteine)TestsFatients should be monitored lor chanqes in blood ressureFatients receivinq hiqh doses or lonqterm treatment should have heatic lunction evaluated eriodically 676TRANYLCYPROMINE (continued)Take at niqht il daytime sedation, take in daytime il overstimulated at niqhtSwitch alter aroriate washout to an SSR or newer antideressantBest Augmenting Agents for Side EffectsTra/odone (with caution) lor insomnia Ben/odia/eines lor insomnia

Sinqle oral or sublinqual dose ol a calcium channel blocker (e.q., nilediine) lor urqent treatment ol hyertension due to druq interaction or dietary tyramineMany side ellects cannot be imroved with an auqmentinq aqentSIDE EFFECTSHow Drug Causes Side EffectsTheoretically due to increases in monoamines in arts ol the brain and body and at recetors other than those that cause theraeutic actions (e.q., unwanted actions ol serotonin in slee centers causinq insomnia, unwanted actions ol noreinehrine on vascular smooth muscle causinq hyertension, etc.)Side ellects are qenerally immediate, but immediate side ellects olten disaear in timeNotable Side EffectsAqitation, anxiety, insomnia, weakness, sedation, di//inessConstiation, dry mouth, nausea, diarrhea, chanqe in aetite, weiqht qainSexual dyslunction 0rthostatic hyotension (doserelated), syncoe may develo at hiqh doses Life-Threatening or Dangerous Side Effectshyertensive crisis (esecially when MA0s are used with certain tyraminecontaininq loods or rohibited druqs)nduction ol mania Rare activation ol suicidal ideation and behavior (suicidality) (shortterm studies did not show an increase in the risk ol suicidality with antideressants comared to lacebo beyond aqe 24)Sei/ures heatotoxicity Weight Gain0ccurs in siqnilcant minority SedationMany exerience and/or can be siqnilcant in amountCan also cause activation What to Do About Side Effectswait wait wait Lower the dose DOSING AND USEUsual Dosage Range8O mq/day in divided doses Dosage FormsTablet 1O mq How to Dosenitial 8O mq/day in divided doses, alter 2 weeks increase by 1O mq/day each1-8 weeks, maximum GO mq/day Dosing Tips0rthostatic hyotension, esecially at hiqh doses, may require slittinq into 8-4 daily dosesFatients receivinq hiqh doses may need to be evaluated eriodically lor ellects on the liverOverdoseBi//iness, sedation, ataxia, headache, insomnia, restlessness, anxiety, irritability, cardiovascular ellects, conlusion, resiratory deression, or coma may also occurLong-Term UseMay require eriodic evaluation ol heatic lunctionMA0s may lose ellcacy lonqterm Habit FormingSome atients have develoed deendence to MA0s (continued) TRANYLCYPROMINE677dextromethorhan, nasal deconqestants (tablets, dros, or sray), haylever medications, sinus medications, asthma inhalant medications, antiaetite medications, weiqht reducinq rearations, "e" ills (see Table 8 alter Fearls)hyoqlycemia may occur in diabetic atients receivinq insulin or oral antidiabetic aqentsuse cautiously in atients receivinq reserine, anesthetics, disullram, metri/amide, anticholinerqic aqentsTranylcyromine is not recommended lor use in atients who cannot be monitored closelywhen treatinq children, carelully weiqh the risks and benelts ol harmacoloqical treatment aqainst the risks and benelts ol nontreatment with antideressants and make sure to document this in the atient's chartBistribute the brochures rovided by the FBA and the druq comanieswarn atients and their careqivers about the ossibility ol activatinq side ellects and advise them to reort such symtoms immediatelyMonitor atients lor activation ol suicidal ideation, esecially children and adolescentsDo Not Usel atient is takinq meeridine (ethidine) l atient is takinq a symathomimetic aqent or takinq quanethidinel atient is takinq another MA0 l atient is takinq any aqent that can inhibit serotonin reutake (e.q., SSRs, sibutramine, tramadol, milnaciran, duloxetine, venlalaxine, clomiramine, etc.)l atient is takinq diuretics, dextromethorhanl atient has heochromocytoma l atient has cardiovascular or cerebrovascular diseasel atient has lrequent or severe headaches l atient is underqoinq elective surqery and requires qeneral anesthesial atient has a history ol liver disease or abnormal liver lunction testsl atient is takinq a rohibited druq l atient is not comliant with a low tyramine dietl there is a roven allerqy to tranylcyromineHow to Stopenerally no need to taer, as the druq wears oll slowly over 2-8 weeksPharmacokineticsClinical duration ol action may be u to 14 days due to irreversible en/yme inhibition Drug InteractionsTramadol may increase the risk ol sei/ures in atients takinq an MA0 inhibitorCan cause a latal "serotonin syndrome" when combined with druqs that block serotonin reutake, so do not use with a serotonin reutake inhibitor or lor 5 halllives alter stoinq the serotonin reutake inhibitor (see Table 1 alter Fearls)hyertensive crisis with headache, intracranial bleedinq, and death may result lrom combininq MA0 inhibitors with symathomimetic druqs (e.q., amhetamines, methylhenidate, cocaine, doamine, einehrine, noreinehrine, and related comounds methyldoa, levodoa, Ltrytohan, Ltyrosine, and henylalanineBo not combine with another MA0 inhibitor, alcohol, or quanethidineAdverse druq reactions can result lrom combininq MA0 inhibitors with tricyclic/tetracyclic antideressants and related comounds, includinq carbama/eine, cycloben/arine, and mirta/aine, and should be avoided excet by exerts to treat dillcult casesMA0 inhibitors in combination with sinal anesthesia may cause combined hyotensive ellectsCombination ol MA0s and ChS deressants may enhance sedation and hyotension Other Warnings/Precautionsuse requires low tyramine diet (see Table 2 alter Fearls)Fatient and rescriber must be viqilant to otential interactions with any druq, includinq antihyertensives and overthecounter couqh/cold rearations0verthecounter medications to avoid include couqh and cold rearations, includinq those containinq 678TRANYLCYPROMINE (continued)Breast FeedingSome druq is lound in mother's breast milk Ellects on inlant unknown mmediate ostartum eriod is a hiqhrisk time lor deression, esecially in women who have had rior deressive eisodes, so druq may need to be reinstituted late in the third trimester or shortly alter childbirth to revent a recurrence durinq the ostartum eriodShould evaluate atient lor treatment with an antideressant with a better risk/benelt ratioSPECIAL POPULATIONSRenal Impairmentuse with caution - druq may accumulate in lasmaMay require lower than usual adult dose Hepatic ImpairmentTranylcyromine should not be used in atients with history ol heatic imairment or in atients with abnormal liver lunction testsCardiac ImpairmentContraindicated in atients with any cardiac imairmentElderlynitial dose lower than usual adult dose Elderly atients may have qreater sensitivity to adverse ellectsReduction in the risk ol suicidality with antideressants comared to lacebo in adults aqe G5 and older Children and Adolescentshot qenerally recommended lor use in children under aqe 18Carelully weiqh the risks and benelts ol harmacoloqical treatment aqainst the risks and benelts ol nontreatment with antideressants and make sure to document this in the atient's chartMonitor atients lacetolace reqularly, articularly durinq the lrst several weeks ol treatmentuse with caution, observinq lor activation ol known or unknown biolar disorder and/or suicidal ideation, and inlorm arents or quardians ol this risk so they can hel observe child or adolescent atients PregnancyRisk Cateqory C |some animal studies show adverse ellects, no controlled studies in humansjhot qenerally recommended lor use durinq reqnancy, esecially durinq lrst trimesterShould evaluate atient lor treatment with an antideressant with a better risk/benelt ratioTHE ART OF PSYCHOPHARMACOLOGYPotential AdvantagesAtyical deression Severe deression Treatmentresistant deression or anxiety disordersPotential DisadvantagesRequires comliance to dietary restrictions, concomitant druq restrictionsFatients with cardiac roblems or hyertensionMultile daily doses Primary Target SymptomsBeressed mood Somatic symtoms Slee and eatinq disturbances Fsychomotor retardation Morbid reoccuation PearlsMA0s are qenerally reserved lor secondline use alter SSRs, ShRs, and combinations ol newer antideressants have lailedFatient should be advised not to take any rescrition or overthecounter druqs without consultinq their doctor because ol ossible druq interactions with the MA0headache is olten the lrst symtom ol hyertensive crisisThe riqid dietary restrictions may reduce comliance (see Table 2 alter Fearls) (continued) TRANYLCYPROMINE679antideressant other than clomiramine simultaneously with an MA0 inhibitor lor atients who lail to resond to numerous other antideressantsuse ol MA0s with clomiramine is always rohibited because ol the risk ol serotonin syndrome and deathAmoxaine may be the relerred trycyclic/ tetracyclic antideressant to combine with an MA0 in heroic cases due to its theoretically rotective 5hT2A antaqonist roertiesl this otion is elected, start the MA0 with the tricyclic/tetracyclic antideressant simultaneously at low doses alter aroriate druq washout, then alternately increase doses ol these aqents every lew days to a week as toleratedAlthouqh very strict dietary and concomitant druq restrictions must be observed to revent hyertensive crises and serotonin syndrome, the most common side ellects ol MA0 and tricyclic/tetracyclic combinations may be weiqht qain and orthostatic hyotensionMood disorders can be associated with eatinq disorders (esecially in adolescent lemales), and tranylcyromine can be used to treat both deression and bulimiaMA0s are a viable secondline treatment otion in deression, but are not lrequently used

Myths about the danqer ol dietary tyramine can be exaqqerated, but rohibitions aqainst concomitant druqs olten not lollowed closely enouqh0rthostatic hyotension, insomnia, and sexual dyslunction are olten the most troublesome common side ellects

MA0s should be lor the exert, esecially il combininq with aqents ol otential risk (e.q., stimulants, tra/odone, TCAs)

MA0s should not be neqlected as theraeutic aqents lor the treatmentresistantAlthouqh qenerally rohibited, a heroic but otentially danqerous treatment lor severely treatmentresistant atients is lor an exert to qive a tricyclic/tetracyclic Table 1.Bruqs contraindicated due to risk ol serotonin syndrome/toxicityDo Not Use:Antidepressants Drugs of Abuse Opioids OtherSSRs MBMA (ecstasy) Meeridine honsubcutaneous sumatritanShRs Cocaine Tramadol ChlorheniramineClomiramine Methamhetamine Methadone BromheniramineSt. John's wort hiqhdose or injected amhetamineFentanyl BextromethorhanFrocarba/ine? 680TRANYLCYPROMINE (continued)Suggested ReadingBaker B, Coutts RT, McKenna KF,SherryMcKenna RL. nsiqhts into the mechanisms ol action ol the MA0 inhibitors henel/ine and tranylcyromine. a review.J Fsychiatry heurosci 1OO2,17.2OG-14.Kennedy Sh. Continuation and maintenance treatments in major deression. the neqlected role ol monoamine oxidase inhibitors.J Fsychiatry heurosci 1OO7,22.127-81.Liman SB, hash K. Monoamine oxidase inhibitor udate. Fotential adverse lood and druq interactions. Bruq Sal 1OOO,5.1O5-2O4.Thase ME, Triyedi Mh, Rush AJ. MA0s in the contemorary treatment ol deression. heurosychoharmacoloqy 1OO5,12.185-21O.Table 2.Bietary quidelines lor atients takinq MA0sFoods to avoid* Foods allowedBried, aqed, smoked, lermented, soiled, or imroerly stored meat, oultry, and lshFresh or rocessed meat, oultry, and lsh, roerly stored ickled or smoked lshBroad bean ods All other veqetablesAqed cheeses Frocessed cheese slices, cottaqe cheese, ricotta cheese, yoqurt, cream cheeseTa and unasteuri/ed beer Canned or bottled beer and alcoholMarmite Brewer's and baker's yeastSauerkraut, kimcheeSoy roducts/tolu FeanutsBanana eel Bananas, avocados, rasberriesTyraminecontaininq nutritional sulement`hot necessary lor Gmq transdermal or lowdose oral seleqilineTable 8.Bruqs that boost noreinehrine. should only be used with caution with MA0sUse With Caution:Decongestants Stimulants Antidepressants with norepinephrine reuptake inhibitionOtherFhenylehrine Amhetamines Most tricyclics FhentermineFseudoehedrine Methylhenidate hRs Local anesthetics containinq vasoconstrictorsCocaine hBRsMethamhetamineModalnil TaentadolArmodalnil