il disturbo schizoaffettivo: criteri diagnostici e trattamento prof. mauro mauri clinica...

Il disturbo Schizoaffettivo: criteri diagnostici e

trattamento

Prof. Mauro MauriClinica PsichiatricaUniversità di Pisa

Do schizoaffective disorders exist all?

More than 100 years ago Kraepelin proposed a very pratical and persuasive solution to a longstanding problem in clinical psychiatry.

To reduce heterogeneity by splitting the perplexing variety of psychopatological signs and symptoms, of patterns of deviant behavior and experiences, of short- and long-term course and outcome of functional disturbances into two major groups:

Dementia Praecox Manic-depressive illness

Acta Psychiatr Scand 2006: 13:369-371. Editorial

In this way, he created the so-called ‘Kraepelinian dichotomy’, which turned out to be clinically useful for subsequent decades.

However, he himself got skeptical subsequently if this simplistic solution really worked in pratice as the number of ‘cases in-between’ were too numerous.

Do schizoaffective disorders exist all? Acta Psychiatr Scand 2006: 13:369-371. Editorial

In 1933, Kasanin first coined this term…


Schizoaffective Disorders

About 70 years ago, the concept of schizoaffective disorders emerged from difficulties in practicing Kraepelin’s dichotomy by separating schizophrenia and affective disorders.


Although originally related to ‘reactive psychoses’ in the Scandinavian tradition, the term became transformed to indicate the intraindividual co-occurrence of both severe affective as well as severe psychotic syndromes, which did not fit in either of Kraepelin’s categories.


Langfeldt G. The prognosis in schizophrenia and the factors influencing the course of the disease. Acta Psychiatr Neurol Scand 1937; Suppl. 13:1–228.


The widespread use of this term reflected the clinical need to consider border-cases separately.

Many clinicians are probably motivated to use this category because of implications on the course of Illness.


Orientamenti attuali

Le evidenze empiriche attualmente disponibili sembrano indicare che i disturbi schizoaffettivi costituiscono un gruppo eterogeneo di condizioni morbose.

Non ha senso affermare che essi, nel loro complesso, rappresentino sempre delle varianti della schizofrenia, oppure delle varianti dei disturbi affettivi maggiori, oppure una terza psicosi.

Definizione

L’espressione “disturbo schizoaffettivo”(1) può essere usata per identificare l’una e/o l’altra delle seguenti situazioni cliniche:

Comparsa successiva e indipendente di una sindrome affettiva e di una schizofrenica (dist. schizoaffettivo tipo I)

Comparsa contemporanea, nel medesimo episodio, di una sintomatologia di tipo affettivo e una di tipo schizofrenico (dist. schizoaffettivo tipo II).

Maj e Perris, 1985

I Disturbi Schizoaffettivi: Modelli Teorici

1.Varietà atipiche della schizofrenia2.Varietà atipiche dei disturbi

affettivi maggiori3.Terza Psicosi4.Continuum Psicotico5.Manifestarsi contemporaneo di

schizofrenia e di un disturbo affettivo maggiore.

Modelli interpretativi dei Disturbi Schizoaffettivi

Modello Binario o dicotomico neo-

kraepeliniano

Modello della terza psicosi

Modello del continuum psicotico

I disturbi schizoaffettivi sono sempre varietà atipiche della schizofrenia o

dei disturbi affettivi maggiori

Almeno una parte dei disturbi schizoaffettivi costituisce un’entità

nosografica distinta dalla schizofrenia e dai disturbi affettivi maggiori

I disturbi schizoaffettivi occupano la parte intermedia di uno spettro ai cui estremi si pongono le forme tipiche di

schizofrenia e di disturbo affettivo maggiore

Il problema della natura dei disturbi schizoaffettivi e dei loro rapporti con la schizofrenia e con i disturbi affettivi maggiori è tuttora controverso.

Schizophrenia Spectrum…Schizophrenia Spectrum almost

certainly includes schizoaffective

disorders (and) should probably

also include at least the psychotic

forms of mania and depression.

(Andreasen, 1995)

I sistemi nosografici hanno

proposto nel tempo criteri ora rigidi

e restrittivi, ora ampi e

comprensivi, senza raggiungere

una delimitazione accettabile sul

piano psicopatologico e clinico.(TSUANG e LOYD, 1986)

Seppure gli estensori delle varie

edizioni del DSM abbiano inteso

segnare confini netti tra psicosi

bipolare e schizofrenica, il

problema rimane irrisolto con le

sue caratteristiche storiche.

Spectrum of Endogenous Psychoses

After Kraepelin E, 1921

Endogenous Psychoses

AffectivePsychoses

SchizoaffectiveDisorder Schizophrenia

BipolarDisorder

PsychoticDepression

BipolarType

DepressiveType

DepressiveEpisodes

NegativeSxs

Schizophrenia with Bipolar Spectrum

Bipolar Spectrum with Psychotic Features

Schizophrenia Spectrum (H.Y. Meltzer, 1995)

Schizophrenia Spectrum

Schizophrenia Schizoaffective Disorder Bipolar Psychotic Disorder Psychotic Depression Schizophreniform Disorder Schizotypal Personality Disorder Schizoid Personality Disorder Paranoid Personality Disorder

Meltzer, 1996

Bipolar-Schizophrenia continuum

Manic-depression and schizophrenia are 2 distinct disorders. (Kraepelin’s)

Proponents of the bipolar continuum theory support the concept of an expanded psychiatric continuum ranging from unipolar to bipolar disorder, to schizoaffective psychosis, all the way to schizophrenia.

Much of the evidence supporting the continuum concept is based upon genetic, biochemical, and pharmacologic findings.

Hans-Jürgen Möller, M.D Bipolar Disorder and Schizophrenia: Distinct Illnesses or a Continuum? (J Clin Psychiatry 2003;64[suppl 6]:23–27)

Il tentativo di tracciare una linea di demarcazione genetica tra disturbi schizofrenici e disturbi affettivi è fallito.

Crow, 1990

Continuum Psicotico

Family linkage studies

•Clinical, familial, and, more recently, genetic linkage studies suggest that overlapping genetic susceptibility might contribute to both schizophrenia and bipolar disorder.

Franck Schürhoff, M.D. et al.,Familial Aggregation of Delusional Proneness in Schizophrenia and Bipolar Pedigrees (Am J Psychiatry 2003; 160:1313–1319)

Family linkage studies

James B. Potash, Suggestive Linkage to Chromosomal Regions 13q31and 22q12 in Families With

Psychotic Bipolar Disorder (Am J Psychiatry 2003; 160:680–686)

•Overlap between bipolar disorder and schizophrenia has long been noted clinically. About 9% of people with schizophrenia have manic syndromes and 25% have depressive syndromes psychotic symptoms—hallucinations and delusions—occur in 58% of people with bipolar I disorder. The existence of a diagnostic category incorporating elements of mood disorder and schizophrenia—schizoaffective disorder—reflects the difficulty that occasionally arises in distinguishing the two illnesses. Evidence for overlapping heritability of bipolar disorder and schizophrenia has emerged from genetic epidemiologic studies

…la mappatura di regioni “sospette” evidenzia una

sovrapposizione delle regioni di linkage per la

Schizofrenia e i Disturbi Affettivi… questi risultati fanno

ipotizzare l’esistenza di geni condivisi da entrambi i

disturbi e la possibilità che questi geni possano

contribuire alle basi molecolari delle psicosi funzionali.

Wildenauer, 1999

This notion is supported by various independent findings.

High degree of genetic transmissibility.Gene mapping for both diseases is in its early stages, but certain susceptibility markers appear to be located on the same chromosomes.

Bipolar disorder and schizophrenia also demonstrate some similarities in neurotransmitter dysfunction.

As further indirect evidence of a possible association, many newer atypical antipsychotic agents approved for the treatment of schizophrenia are also proving useful for bipolar disorder.

Hans-Jürgen Möller, M.D Bipolar Disorder and Schizophrenia: Distinct Illnesses or a Continuum? (J Clin Psychiatry 2003;64[suppl 6]:23–27)

NeuroanatomyVarious structural abnormalities have been found in imaging studies of patients with bipolar disorder or schizophrenia, although none has yet provided any clear answers regarding a possible relationship between the 2 disorders.

Ventricular enlargmentPrefrontal atrophy Disgenesy of hippocampal structureGlycocorticoid hypersecretionMuscle-scheletal anomalies Riduction of number of 5-HT 2 receptors Altered eye movementsCognitive deficits

…nonostante una ampia sovrapposizione delle anomalie

strutturali nelle cosiddette psicosi endogene, la corteccia

associativa, il sistema limbico e le strutture asimmetriche

sono maggiormente coinvolte nella Schizofrenia, mentre

lievi anomalie strutturali nei nuclei della base, specie nel

nucleo accumbens e nell’area ipotalamica, potrebbero

avere un ruolo cruciale nei Disturbi dell’Umore.

Baumann, 1999

La diagnosi di schizofrenia basata solo sui sintomi è spesso erronea.

Pope & Lipinsky, 1978

Sebbene gli aspetti sintomatologici della schizofrenia si collochino in primo piano rispetto ad altre manifestazioni nell'esame del quadro clinico globale, non emergono, alla luce dei più recenti contributi, sintomi patognomonici o combinazioni di sintomi in grado di differenziare la malattia da altre patologie di confine.

(Clayton, 1986)

'I sintomi della mania o degli stati misti sono spesso simili a quelli della schizofrenia; si tratta di un'ampia zona di confine in cui la diagnosi diviene incerta...'

I confini della schizofrenia e dei disturbi bipolari

Cassano & Mauri, 1990

• Deliri Grandiosità Riferimento Persecuzione Somatici Nichilistici Bizzarri Sistematizzati

• Allucinazioni Uditive Visive Olfattive Tattili

Sintomi Psicotici nella Mania

(McElroy, 1995)

• Disturbi formali del pensiero

• Sintomi di primo rango

• Catatonia

50% con almeno un delirio

15% con almeno una allucinazione

20% con disturbi formali del pensiero

Episodi maniacali e sintomi psicotici

Goodwin and Jamison, 1990

Altrettanto erronea può essere

la diagnosi fondata sull'epoca,

sulla modalità di esordio,

sull'evoluzione sugli esiti.

100

80

60

40

20

0

Number of Psychotic Symptoms as a function of Age at onset in Bipolar Patients

Age at onset of Bipolar Illness<20 20-29 30-39 =/>40

No psychoticsymptoms

1-2 psychoticsymptoms

>3 psychoticsymptoms

Rosen et al., 1993

Atypical and subthreshold forms of bipolarity in relation to age at onset

Early Onset (in childhood & adolescence)

Ebephrenia like mania Abrupt & temporary psychomotor

agitation Pseudo-conduct disorder mania

Mild elation Marked exhaustibility of the

manifestations Partial symptomatology Prevalence of dysphoria over euphoria Paranoid content

Late Onset (in elderly)

Le modificazioni di personalità, il decorso

subcronico, la patologia intercritica persistente, il

decadimento della performance sociale,

rappresentano aspetti comuni a disturbi mentali

diversi. Pertanto anche la specificità del criterio

centrato sulla sindrome deficitaria persistente, è

in discussione.

Enduring deficit syndrome

…la patologia affettiva è esclusa dalla

schizofrenia sulla base di un arbitrario

approccio gerarchico; gli aspetti di

decorso e di durata sono stabiliti in

modo del tutto convenzionale.

CARSON, 1984

Patologia affettiva e Schizofrenia

Settanta anni dopo Bleuler siamo ancora incapaci di affermare con sicurezza che la schizofrenia rappresenta un'entità unitaria, o più precisamente che i comportamenti convenzionalmente associati con questo termine derivano da un unico nucleo o deficit.

Carson, 1984

L’ impiego di una categoria

diagnostica è in rapporto alla

disponibilità di trattamenti efficaci. L’area di un disturbo mentale tende

pertanto ad espandersi o a ridursi.

Rapporti tra diagnosi e trattamento

Due disturbi distinti ?

Due aspetti sindromici dello stesso disturbo?

On a clinical level the overlap between the sindromes of schizophrenia and affective disorders are too broad to be captured by the intermediate diagnosis of schizoaffective disorders.


In contrast to its clinical popularity, research investigations in this diagnostic category -although operational definitions became available - remained relatively rare as it becomes from a PubMed search (search terms in titles: schizoaffective disorder =230 citations; schizophrenia =13.297; bipolar disorder =2.355; during a 10-year period 1995-2005).


The diagnosis ‘schizoaffective disorder’ has not yet been unequivocally defined after more than 70 years.


It is more appropriate to integrate categorical diagnostic concepts with dimensions: a psychotic, a manic and a depressive one, which allows graduations and overlaps.


Treatment of schizoaffective disorders

Condition Treatment

Acute Episodes

Mainly affective episodes

Schizomanic (-bipolar) Li, antipsychotics (when highly excited)

Schizodepressive Antidepressants, Antipsychotics (Olz, Ris, Zip.)

Mainly schizophrenic

Schizomanic Antipsychotics

Schizodepressive Antipsychotics, ECT

Long-Term Treatment

Mainly affective

Schizobipolar Li, Carbamazepine

Schizodepressive Carbamazepine, Li

Mainly schizophrenic

Schizobipolar Antipsychotics (Olz)

Schizodepressive Antipsychotics

Maj M, Perris C. Patterns of course in patients with a cross-sectional diagnosis of schizoaffective disorder. J Affect Disord. 1990 Oct;20(2):71-7.

For mainly affective schizomanic episodes lithium and antipsychotics are the best evaluated medications and should be the first line treatment. In highly excited schizomanic syndromes antipsychotics are superior to lithium.

In mainly schizophrenic schizomania antipsychotics are probably the best choice, although there are only few data.

Treatment of schizoaffective disorders: Acute Episodes

A difficult to treat condition is the schizodepressed syndrome. Predominantly affective schizodepressed episodes might benefit from treatment with antidepressant or antipsychotics.

Olanzapine, risperidone and ziprasidone promising results with regards to schizodepression have to be viewed as preliminary with regard to schizoaffective disorder.

Electroconvulsive therapy has not been sufficiently studied in this sub-group. However, given its efficacy in major depression and in schizophrenia it might be a promising treatment option.

Treatment of schizoaffective disorders: Acute Episodes

First choice for predominantly affective schizobipolar patients is lithium. Carbamazepine was as effective as lithium in one RCT but is less well studied.

From one RCT, however, it appears that carbamazepine might be superior to lithium in the sub-group of mainly affective schizodepressive patients.

A family history of bipolar disorder and pronounced suicidality also supports lithium. This, however, is an analogy to bipolar disorder and has not been shown for SAD.

In pts with mainly schizophrenic SAD antipsychotics are the long-term treatment of choice and, in the absence of sufficient data, treatment decision have to be made in analogy to schizphrenia.

Treatment of schizoaffective disorders: long-term treatment

For SAD, olanzapine is the only drug has been tested in a RCT in long-term treatment. From observational studies there are encouraging results for the use of clozapine in SAD long-term treatment.

Combination treatment is increasingly common (1). However, it has not been well studied (2). For SAD, therefore, combination should be deployed only after monoterapy fails.

Combination of lithium and haloperidol(3) as well as lithium and carbamazepine(4) have been reported to be safe and affective.

Treatment of schizoaffective disorders: long-term treatment

1) Kupfer et al. Demographic and clinical characteristics of individuals in a bipolar disorder case registry. J Clin Psychiatry. 2002 Nov;63(11):1045-6

2) Baethge C et al. Long-term combination therapy versus monotherapy with lithium and carbamazepine in 46 bipolar I patients.J Clin Psychiatry. 2005 Feb;66(2):174-82

3) Lowe MR and Batchelor DH. Lithium and neuroleptics in the management of manic depressive psychosisHuman psychopharmacology, 5, 267-74

4) Bocchetta A.Carbamazepine augmentation in lithium-refractory bipolar patients: a prospective study on long-term prophlyactic effectiveness. Clin Psychopharmacol. 1997 Apr;17(2):92-6.

Conclusion … ‘patients with schizoaffective disorders in

their majority have in fact a different social adaption, a different symptomatology, and a different prognosis than pure schizophrenic patients. It is useful for the physician and it is a hope for the patient to know that. A useful clinical diagnosis which concerns millions of people can not be abandoned in favour of permanently changing theoretical concepts’.

A. Marneros: Letters to the Editor. Acta Psychiatr Scand 2007: 115: 162–165

il disturbo schizoaffettivo: criteri diagnostici e trattamento prof. mauro mauri clinica...

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