Dincolo de tristee:

Recunoaterea i remisiunea simptomelor fizice i emoionale din depresie

DEPRESIA DIN PERSPECTIV ISTORICscrierile biblice Iliada i Odissea tragediile lui Esquil i Sofocleperioada preclinic - Hipocrate perioada clinic - Robert Burton "Anatomy of Melancholy" (1621)perioada modern i contemporan Kraepelin, Freud, Schneider, Leonhard, Beck

*Depresie major.1. World Health Organization. The World Health Report 2001: Mental Health: New Understanding, New Hope. Geneva, Switzerland: World Health Organization; 2001.2. Michaud CM, et al. JAMA. 2001;285:535-539.3. Kessler RC, et al. Arch Gen Psychiatry. 1994;51:8-19.4. Bostwick JM, Pankratz VS. Am J Psychiatry. 2000;157:1925-1932.5. Murphy J, et al. Arch Gen Psychiatry. 1987;44:473-480.MDD* este o problem de sntate publicPrincipala cauz de disabilitate din SUAa 4 a cauz de afectare a sntiia 2 a cauz n 20201 din 6 indivizi au experiena unui episod depresiv major pe parcursul vieii3MDD este potenial fatal4,58% dintre pacieni cu MDD care necesit spitalizare pot comite suicidul4Depresia crete riscul general de mortalitate5

Date epidemiologice generaleIncidena depresiei - 80 - 200/100.000/an la populaia de sex masculin i 250 i 7.800/100.000/an la femeiVrsta medie a debutului - spre sfritul celei de-a treia decad de via, dar boala poate debuta la orice vrst, ncepnd nc din copilrie

Gender Differences

Factori depresogeniGrupe nosologiceDepresiisomatogeneendogenepsihogene1234Boli cerebrale:demene presenile i senile, vasculopatii cerebrale, tumori cerebrale, epilepsie, traumatisme cranio-cerebrale.Parkinsonism -encefalite, etc.Depresii organiceBoli extracerebrale:infecii virale, intoxicaii cronice, anemie, deficit de vit. B, endocrinopatii (diabet, hipotiroidism, boala Addisson, b. Cushing, Feocromocitom, etc.), colagenoze, tratamente ndelungate cu preparate farmacogene, antihipertensive, methyldopa, hormoni sexuali, tranchilizante, anticoncepionale, cortizonice, etc., miocardiopatii, suferine digestive, pielonefrite cronice, porfirieDepresiiSimptomaticeFarmacogeneForma de graniDepresia puerperal.Factori predispozani ereditari (vulnerabilitate).Factori declanatori somaticiDepresii monopolare (episod unic sau episoade recurente).Depresii bipolare (alterneaz episoade depresive i maniacale).Depresii tardive (melancoliforme).Schizodepresii.Factori declanatori psihogeniUnul sau mai multe evenimente stresante de via.ncordare emoional prelungit.Psihotraume recente i conflicte intrapsihice tensional- nedescrcate.Distimii endoreactiveEpuizareNevroze reactive

Depresia: O afeciune sistemicManifestri emoionale i fizice

DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000. Kroenke K, et al. Arch Fam Med. 1994;3:774-779.cefalee obosealdisgripniiameeliDureri toraciceDureri articulareDureri de spateAcuze gastroenterale (grea, vrsturi, constipaie, diaree, flatulen)Disfuncii sexualeProbleme menstrualeDispoziie depresivAnhedonieLips de speranautodepreciereMemorie afectatDificulti prosexiceAnxietateGnduri negre

*Physical symptoms included fatigue; disturbed sleep; menstrual problems; dizziness; GI complaints (nausea, vomiting, gas, constipation, diarrhea); headache; joint or limb pain; back pain; abdominal pain; chest pain; sexual dysfunction/apathy; and others.Kroenke K, et al. Arch Fam Med. 1994;3:774-779.0 to 1(n=215)2 to 3(n=225)4 to 5(n=191)6 to 8(n=230)9(n=139)Simptome fizice multiple pot indica depresia

SimptomFrecvenDispoziie depresiv95-100%Insomnie95%Tulburri de concentrare90%Idei autolitice80%Fatigabilitate75%Inapeten80%Disperare50%Idei delirante35%Tentativ autolitic15%

Criterii de diagnostic pentru episodul depresiv major 1. indispoziie depresiv (la copii i adolesceni, ea poate fi iritabil) cea mai mare parte a zilei aproape n fiecare zi, relevat, fie de relatarea subiectiv, fie de observarea altora; 2. diminuarea evident a interesului sau plcerii pentru toate, sau aproape toate activitile, n cea mai mare parte a zilei, aproape n fiecare zi (exprimat subiectiv sau observarea apatiei de ctre alii, n majoritatea timpului);3. pierderea sau creterea ponderal n absena unei diete (de exemplu, peste 5% din greutate ntr-o lun), ori scderea sau creterea apetitului, aproape n fiecare zi, la copii se consider incapacitatea de a ctiga n greutate plusul expectat; 4. insomnie sau hipersomnie, aproape n fiecare zi;

Criterii de diagnostic pentru episodul depresiv major5. agitaie sau lentoare psiho-motorie, aproape zilnic, observat de alii i nu simplul sentiment subiectiv de nelinite sau lentoare; 6. oboseal sau pierderea energiei, aproape zilnic;7. sentimente de devalorizare sau de culp excesiv sau inadecvat (ce poate fi delirant) aproape zilnic (nu numai autoreproul sau culpa de a fi bolnav);8. diminuarea capacitii de a gndi, de a se concentra i indecizia aproape n fiecare zi (exprimat subiectiv sau observat de alii); 9. idei recurente de moarte (nu frica de a muri), idei sau preocupri suicidare recurente fr un plan anume, sau o tentativ de suicid ori un plan anume pentru realizarea suicidului.

Criterii de diagnostic pentru episodul depresiv majorSimptomele nu ndeplinesc criteriile pentru episodul mixt

Simptomele produc tulburri semnificative clinice, sociale, ocupaionale

Nu sunt efectele directe psihologice ale substanelor (drog, abuz de medicamente) sau condiii medicale generale (ex. hipotiroidism)

Nu se datoreaz unor pierderi mari (pierderea unei persoane iubite)

DIAGNOSTIC DIFERENIALTristeea normalDoliul Anxietatea i panicaSchizofreniaTulb somatoformTulb legate de stress

DIAGNOSTIC DIFERENIALAFECIUNI SOMATICEBoli neurologice epilepsie, AVC, Parkinson, scleroza multiplBoli cardiovasculareCancerBoli endocrine

DIAGNOSTIC DIFERENIALRezerpina Alfa-metildopaSevraj amfetamineBetablocante Fenobarbital

Contraceptive oraleSteroizi Tamoxifene Cimetidin Acetazolamid

Obstacole n recunoaterea depresieidepresie mascatcomorbiditatea cu alte boli vrstnici alian ntre pacient i medic mpotriva depresiei (tacit collusion)

Clinical Practice Guideline, 5: Depression in Primary Care, 2: Treatment of Major Depression; 1993. AHCPR publication 93-0551. Frank E, et al. Arch Gen Psychiatry. 1991;48:851-855.Tratamentul depresiei

RspunsReducerea clinic semnificativ a severitii simpt n comparaie cu baseline

RemisiuneAbsena sau aproape absena simptomelor i resturarea funcionriiRecdereReapariia simptomelor depresive n timpul continurii tratamentuluiRecurenNou episod depresiv aprut dup o remisiune susinut a unui episod precedent

DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000. Rush AJ, Trivedi MH. Psychiatr Ann. 1995;25:704-705, 709.Remisiunea este scopul tratamentuluiSimptome minime sau absente (HAM-D17 7)Restaurarea integral a capacitii de funcionare n toate domeniile vieiimunc, hobbies/interese personale, relaii sociale Pacientul nu poate fi deosebit de indivizii fr depresie

Adapted from: Kupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28-34.Remisiunea simptomelor este poarta ctre o recuperare susinut

Judd LL, et al. Am J Psychiatry. 2000;157:1501-1504.Paykel ES, et al. Psychol Med. 1995;25:1171-1180. Thase ME, et al. Am J Psychiatry. 1992;149:1046-1052.Miller IW, et al. J Clin Psychiatry. 1998;59:608-619.Murphy JM, et al. Arch Gen Psychiatry. 1987;44:473-480.6.Everson SA, et al. Arch Intern Med. 1998;158:1133-1138.Lustman PJ, et al. Diabetes Care. 2000; 23:934-942.de Groot M, et al. Psychosom Med. 2001;63:619-630.Frasure-Smith N, et al. JAMA. 1993;270:1819-1825.Penninx BWJH, et al. Arch Gen Psychiatry. 2001;58:221-227. Vaccarino V, et al. J Am Coll Cardiol. 2001;38:199-205.Ickovics JR, et al. JAMA. 2001;285:1466-1474.Riscurile n cazul n care nu se obine remisiuneaRisc crescut de recdere sau recuren1-3Episoate mai frecvente i de mai lung durat1Scurtarea perioadelor dintre episoade1Afectare continu socio-profesional4Crete mortalitatea5 i morbiditate/mortalitate prin AVC,6 diabet,7,8 IM,9 CIC,10 IC,11 HIV,12 etc.

*P

*Remission=HAM-D17 7.Based on odds ratio for DSM-IV major depression at 6-, 9-, 12-, 18-, and/or 24-month assessments for remitters at 3 months (OR=0.32; 95% CI 0.18-0.54).Simon GE, et al. WHO Bulletin. 2000;78:438-445.Outcome at 3 monthsRelapse/recurrence of MDD over next 2 years (%)Non-remisiunea este factor de prognostic nefavorabil

American Psychiatric Association. Practice Guideline for the Treatment of Patients With Major Depression. 2nd ed. Washington, DC; 2000.Alegerea tratamentului: Scopul este remisiuneaAntidepresive care i-au demonstrat eficacitateaDoze adecvateAsigur compliana pacientuluiIdeal este s previi urmtorul episod

Phenelzine Isocarboxazid TranylcypromineClomipramineNortriptyline Amitriptyline DesipramineFluoxetine SertralineParoxetine Fluvoxamine CitalopramNefazodone Mirtazapine Venlafaxine1950s1960s1970s1980s1990sMaprotiline AmoxapineImipramine (1957)Spectru largBupropion2000+EscitalopramDuloxetineAciune mai selectivAntidepresive moderneEvoluia antidepresivelor

dispoziie, emoii, funcii cognitiveMotivaieSexApetitAgresivitateAnxietateIritabilitateEnergie InteresImpulsivitateInstincteNorepinefrinaSerotoninaDopaminaNeurotransmitorii care sunt implicai n fiziopatologia depresieiStahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 2nd ed. Cambridge, UK: Cambridge University Press; 2000:152.

intele neuroanatomice ale antidepresivelor

Clasa de antidepresiveDozare (mg/zi)Inhibitorii de monoamin-oxidaz (IMAO)Phenelzine45-90Inhibitorii recaptrii monoaminelorClomipraminaAmitriptilinaImipramina50-150100-300100-300Inhibitorii reversibili ai monoamin-oxidazei tip A (RIMA)Moclobemide300-600Inhibitorii selectivi ai recaptrii serotoninei i noradrenalinei (SNRIs)Venlafaxina150-300Inhibitorii selectivi ai recaptrii serotoninei (SSRIs)CitalopramFluoxetinaFluvoxaminaParoxetinaSertralina20-6020-4050-15020-5050-150Inhibitorii selectivi ai recaptrii noradrenalinei (NARIs)Reboxetina4-8Modulatorii receptorilor serotoninergici (SRMs)NefazodoneMirtazepina300-60015-45

Efecte secundareTricicliceefecte anticolinergice - uscciunea gurii, constipaie, retenie urinar, tulburri de vedere, palpitaii i tahicardie; precauie la pacieni cu glaucom, retenie urinar, stenoz piloric sau hipertrofie de prostattoxicitatea cardiac sever, cu tulburri de conducere sau aritmiimodificri n greutatehipotensiune arterialefect iritativ gastricreacii alergice cutanatemodificri ale libido-ului, impoten, ginecomastie i galactoreeContraindicaiile triciclicelor sunt: infarct miocardic acut, tulburri de ritm i conducere, insuficien coronarian, hepatopatie sever, manie, graviditate, alptareAntidepresivele triciclice sunt letale n supradozare

Efecte secundareSSRIs

GreaCefaleeNervozitateSedareInsomnie

Gur uscatDiareeFatigabilitateAnxietateAnorexieDisfuncii sexuale

Sindromul serotoninicse datoreaz creterii concentraiilor serotoninei plasmatice pn la niveluri toxicepotenial fatal - n ordinea manifestrilor (pe msur ce starea se agraveaz): diaree nelinite agitaie extrem hiperreflexie i instabilitatea sist autonom mioclonus convulsii hipertermie, frisoane, rigiditate, delir com, status epilepticus colaps cardiovascular i exitus

Shelton RC. Harv Rev Psychiatry. 2000;8:161-174.Dincolo de membrana celular: Aciunea intracelular a antidepresivelorEfectele asupra receptorilor determin modificri intracelulareApar cascade enzimatice care influeneaz producerea sau inhibiia unor geneNorepinefrina i serotonina sunt elementele centrale

Delgado PL, et al. Biol Psychiatry. 1999;46:212-220.Delgado PL, Moreno FA. J Clin Psychiatry. 2000;61(suppl 1):5-12.NRI respondersNondepressed subjects5-HTdepletionSymptoms returnSSRI responders5-HTdepletion5-HTdepletionNo symptoms appearNEdepletion NEdepletion NEdepletion No symptoms returnNo symptoms appearSymptoms returnNo symptoms return

1.Danish University Antidepressant Group. J Affect Disord. 1990;18:289-299.2.Clerc GE, et al. Int Clin Psychopharmacol. 1994;9:139-143.3.Poirier M-F, Boyer P. Br J Psychiatry. 1999;175:12-16.4.Thase ME, et al. Br J Psychiatry. 2001;178:234-241.5.Meoni P, et al. Presented at: World Congress of Biological Psychiatry; July 2001;Berlin, Germany. Beneficiile SNRIsTrateaz un spectru larg de pacieni1-3

Se atinge remisiunea

Afecteaz att simptomele psihice ct i cele fizice5

PsihoterapiaDepresia uoar de elecie

Depresia moderat alternativ (+/- chimioterapie)

Depresia major tratament adjuvant

Tipuri de intervenii psihoterapeuticeTerapia cognitiv-comportamentalPsihanalizaHipnozaPsihoeducaiaaltele

**Key PointThe high burden of disease associated with major depressive disorder (MDD) underscores the urgency for early and aggressive treatment of patients experiencing depressionBackgroundThe World Health Organization (WHO)1 has ranked MDD as the leading cause of health-related disability as well as the fourth greatest cause of global illness burden. Global illness burden refers to assessments of fatal and nonfatal health outcomes in populations worldwide. It is frequently measured in disability-adjusted life years (DALYs), which is the sum of the years of life lost due to premature mortality and years of life lost due to disabilityProjections of future burden of disease data2 predict that MDD will be the second leading cause of death in 2020, dominated only by ischemic heart diseaseIt is estimated that approximately 1 in 6 individuals will experience a major depressive episode in his/her lifetime3Approximately 8% of patients with MDD severe enough to require hospitalization eventually die from suicide4Results from a 16-year prospective longitudinal study showed that the risk of all-cause mortality was approximately three- to five-fold higher in patients with depression (with or without concomitant anxiety)5References1.World Health Organization. The World Health Report 2001: Mental Health: New Understanding, New Hope. Geneva, Switzerland: World Health Organization; 2001.2.Michaud CM, et al. JAMA. 2001;285:535-539.3.Kessler RC, et al. Arch Gen Psychiatry. 1994;51:8-19.4.Bostwick JM, Pankratz VS. Am J Psychiatry. 2000;157:1925-1932.5. Murphy J, et al. Arch Gen Psychiatry. 1987;44:473-480.

*Key PointPhysical symptoms may be the major mediating morbid event leading a patient to seek treatmentBackgroundPatients with MDD can present with a variety of emotional and physical signs and symptomsIn addition to depressed mood and anhedonia, emotional symptoms associated with MDD include feelings of hopelessness, low self-esteem, impaired memory, difficulty concentrating, anxiety, and preoccupation with negative thoughtsPatients with MDD also may present with a wide variety of physical complaints; indeed, physical symptoms are the predominant complaint among patients seeking treatment in general medical settingsAs these symptoms are general in nature, it is important to obtain a complete medical history and to rule out other physical illnesses to ensure an accurate diagnosis of depressionReferences1. DSM-IV-TR. Washington, DC: American Psychiatric Association; 2000.2. Kroenke K, et al. Arch Fam Med. 1994;3:774-779.*Key PointThe number of physical symptoms is highly predictive for psychiatric disordersBackgroundAn outpatient mental health survey of 1,000 adult primary care patients examined how the number and type of physical symptoms are related to psychiatric disorders and functioning The likelihood of a diagnosis of a mood or anxiety disorder was 2 to 3 times greater in patients reporting 1 or more physical symptomsThe likelihood of a psychiatric disorder increased dramatically with increasing numbers of physical symptoms; more than 80% of patients who reported 9 or more physical symptoms had a psychiatric diagnosisThe prevalence of a mood disorder increased from 2% for patients with 0 to 1 symptom, to 60% for patients with 9 or more physical symptomsMultiple or unexplained symptoms may signify a potentially treatable mood or anxiety disorderReferenceKroenke K, et al. Arch Fam Med. 1994;3:774-779.

*Key PointPossible outcomes during treatment for depression include response, remission, relapse, and recurrenceBackgroundResponse is generally defined as a clinically significant reduction in baseline symptom severity. A common operational definition in clinical research is a 50% decrease from baseline scores on the Hamilton Depression Rating Scale (HAM-D17)Remission is generally defined as an absence or near absence of depressive symptoms and restoration of functioning in all life domains. A common operational definition in clinical research is a HAM-D17 score of 7, although various other definitions have been used in clinical studiesA relapse occurs when symptoms of the current episode return and are severe enough to meet syndromal criteria A recurrence is a new episode of depression following sustained remission of the previous episodeInconsistencies in the description of outcomes have compromised research on this disorder. Standardization of definitions for critical outcomes measures will lend validity to studiesReferencesClinical Practice Guideline, 5: Depression in Primary Care, 2: Treatment of Major Depression; 1993. AHCPR publication 93-0551. Frank E, et al. Arch Gen Psychiatry. 1991;48:851-855.*Key PointThe goal of depression treatment is remission, defined as minimal or no symptoms and a return to normal functioning in all life domainsBackgroundTreatment for major depression must extend beyond simply diminishing symptoms to a lower level of suffering; the ultimate goal should be remission of symptoms with full restoration of functioningRemission of symptoms occurs when the individual has improved to a level at which he or she has minimal or no symptoms. A widely accepted operational definition of symptomatic remission is a HAM-D17 score of 7Sustained remission of symptoms is necessary for restoration of normal psychosocial and occupational functioning. Patient-specific operational markers such as returning to work, resumption of hobbies, personal interests, and personal relationships can be used to gauge functional normality in all life domainsPatients who have achieved remission of symptoms generally cannot be distinguished from persons without the disorderReferencesDSM-IV-TR. Washington, DC: American Psychiatric Association; 2000. Rush AJ, Trivedi MH. Psychiatr Ann. 1995;25:704-705, 709. *Key PointRemission is the goal of acute-phase treatment; prevention of relapse and recurrence is the goal of continuation- and maintenance-phase treatmentBackgroundThe acute phase of treatment begins when the patient first presents with an episode of depression, and the minimal treatment goal is to elicit a response to medication or psychotherapy, or both. From a clinical perspective, this phase of treatment is most successful if it results in a remission rather than merely a response. Note that remission can occur beyond the acute phase, especially in chronic depressionThe goal during the continuation phase is to provide continuing sustained remission and to prevent relapse (i.e., a return of symptoms of the major depressive episode)Likewise, the minimal goal during maintenance treatment is to prevent a recurrence (i.e., a new episode of major depression) and preferably to provide continuing sustained remissionAttainment of initial remission and then sustained remission is the best way to prevent relapse and recurrenceReferenceKupfer DJ. J Clin Psychiatry. 1991;52(suppl 5):28-34.

*Key PointFailure to achieve remission is associated with many negative outcomesBackgroundAchievement of response rather than remission is associated with a substantially greater risk of relapse/recurrence1-3Patients who do not achieve remission have been shown to experience more chronic depressive episodes1 shorter durations between episodes1Nonremitters continue to suffer from impaired psychosocial functioning (e.g., work and relationships)4Finally, failure to achieve remission has been associated with increased morbidity and mortality with many other general medical conditions5-12References1.Judd LL, et al. Am J Psychiatry. 2000;157:1501-1504.2.Paykel ES, et al. Psychol Med. 1995;25:1171-1180. 3.Thase ME, et al. Am J Psychiatry. 1992;149:1046-1052. 4.Miller IW, et al. J Clin Psychiatry. 1998;59:608-619.5.Murphy JM, et al. Arch Gen Psychiatry. 1987;44:473-480. 6.Everson SA, et al. Arch Intern Med. 1998;158:1133-1138. Lustman PJ, et al. Diabetes Care. 2000; 23:934-942.de Groot M, et al. Psychosom Med. 2001;63:619-630.Frasure-Smith N, et al. JAMA. 1993;270:1819-1825.Penninx BWJH, et al. Arch Gen Psychiatry. 2001;58:221-227.Vaccarino V, et al. J Am Coll Cardiol. 2001;38:199-205.Ickovics JR, et al. JAMA. 2001;285:1466-1474.*Key PointFailure to achieve remission of symptoms is a strong predictor of subsequent relapse/recurrenceBackgroundThis prospective, longitudinal, naturalistic, follow-up study evaluated the impact of residual symptoms on relapse in psychiatric inpatients or outpatients (aged 18 to 65 years) with primary unipolar major depression. Patients were treated with usual care by their physicians (including pharmacotherapy and/or electroconvulsive therapy) and followed to the point of remission and thereafter or until 15 months had elapsed without achievement of remission. Remission was defined as 2 consecutive months below the Research Diagnostic Criteria (RDC) for definite major depressionBy 15 months, 60 patients had remitted below the RDC for major depression. Residual symptoms (i.e., a response without remission, defined as a HAM-D17 score 8) were present in 32% (n=19) of the 60 patients. The other 41 patients had achieved full remission with no residual symptoms (i.e., they had HAM-D17 scores 7)Failure to achieve remission was a strong predictor of subsequent early relapse (defined as a return to symptoms meeting the RDC for definite major depression for 1 month). Significantly more patients (P