Long term outcome and prognosis in schizophrenia

Manjeet Singh

History

• In the pre-kraeplelinian era secondry dementia was considered the outcome of most psychoses now diagnosed as schizophrenia.

• Kraepelin pointed out that the deficiency was more in the field of emotion and volition, less in that of judgement or memory.

• In bleuler’s view the disturbance of intelligence could not be adequately described as dementia.

History

• In 1903 Kraepelin noticed that the basic form of dementia praecox and manic depressive insanity in the Javanese were essentially the same as in Europe.

• In a 1953 monograph published by the WHO, John Carothers claimed that the paucity of structural delusional content and lack of systematization of delusion in the African could be explained by congenital underdevelopment of frontal lobe of brain.

Outcome

• Short term - < 2 years follow-up.• Mid term - 2-5 year follow-up.• Long term - >5 years follow-up

Dimensions of outcome

• Outcome is a multidimensional construct that a minimum requires description of domains for:

1. Clinical (symptoms and treatment).2. Psychosocial function.

Functional outcome domains

• Social• Occupational• Independent living• Rehabilitation success• Substance abuse

Terminology of outcome

• Define outcome in terms of:

1. Response 2. Remission 3. Recovery 4. Relapse

Response

• Response is some relief of symptoms and some improvement in functioning. The term ‘response’ implies that this improvement arises from treatment, usually because it is associated in time with that treatment.

Remission• Remission is a period of complete relief of

symptoms and a return of full functioning, which may be brief.

• Remission criteria define remission as a low-mild symptom intensity level, where such absent, borderline, or mild symptoms do not influence an individual’s behavior. *

*Liberman RP, Kopelowicz A, Venture J, Gutkind D: Operational criteria and factors related to recovery from schizophrenia. Int Rev Psychiatry 2002; 14:256–272

Recovery

• “Mental health recovery is a journey of healing and transformation enabling a person with a mental health problem to live a meaningful life in a community of his or her choice while striving to achieve his or her potential.”

Or • Is a period of complete relief of symptoms and a

return of full functioning, which is likely to be longer term.

Relapse• Is the return of symptoms, satisfying the diagnostic

criteria for the disorder, after a patient has either responded or remitted, but before recovery.

• According to Johnstone, relapse could also be defined as Type I, the reappearance of schizophrenic symptoms in a patient who has been free of them following the initial episode, and Type II, the exacerbation of persistent positive symptoms*.

*Johnstone EC. Relapse in schizophrenia: what are the major issues? In: Hawton K, editor. Practical problems in clinical psychiatry. Oxford: Oxford University Press; 1992;159-71.

Recurrence

• Recurrence is the return of symptoms, satisfying the diagnostic criteria for the disorder, after the patient has recovered.

Need for follow-up study

• To know natural history of disease.• Course of disease.• Outcome of disease.• Cultural variation of disease course and

outcome.• Effect of drugs on disease progression.

List of selected course and outcome studies in schizophrenia 1972-2005

Author Country Sample size

Length of F/U

Proportion good outcome

Bleuler (1972) Switzerland 208 23 20% remission , 33% mild defect

Tsung et al. (1979)

USA 186 35 46% recovered or improve significantly

Ciompi (1980) Switzerland 289 37 20% recovered, 43% definitely improved

Huber et al. (1980)

Germany 502 22 26% recovered 31% remission with mild defect

Harding et al. (1987)

USA 118 32 62% recovered or improved significantly

Ogawa et al. (1987)

Japan 140 21-27 31% recovered, 46% improved

Author Country Sample size Length of F/U

Proportion good outcome

Shepherd et al. (1989)

UK 107 5 22% rcovered, no relapse

Johnstone et al. (1990)

UK 530 3-13 14% excellent, 18.5% very good social adjustment

Caron et al. (1991)

USA 79 5 17% complete remission

Marneros et al. (1992)

Germany 249 25 Full remission in 24% (broad), 7% pure schizo.

Thara et al. (1994)

India 90 (1st onset) 10 12% complete recovery, 62% remission

Mason et al. (1995)

UK 67 13 17% complete recovery, 52% remission

Wieselgren & Lindstrom (1996)

Sweden 120 5 30% good outcome

Wiersma et al. (1998)

Holland 82 15 27% complete, 50% partial remission

Author Country Sample size Length of F/U

Proportion good outcome

Ganev et al. (1998)

Bulgaria 60 16 32% complete, 5% partial remission

Gureje & Bamidele (1999)

Nigeria 120 13 22% unimpaired 19% some impairment

Finnerty et al. (2002)

Ireland 67 (1st onset) 15 35% complete remission, 46% partial remission

Thara (2004) India 90 (1st onset) 20 6% complete recovery, 15% clinically stable

Lauronon et al. (2005)

Finland 91 (birth cohart members)

To age 31 yr 4% complete recovery, 3% partial remission

Indian study author Outcome

Clinical Social, occupational

Johnson S et al/ 2012/ vellore India

68% remitted, 24% had at least one additional psychotic episode

Median WHO-DAS score 8

Srivastava A et al /2009/ Mumbai India

100% had PANSS positive score <21, 88% had PANSS negative score <21

61.7% had GAF > 80

Suresh et al/ 2012/ rural Karnataka India

N/A 60% of patient had mild/no disability in work

Verghese A et al/ 1989/ Chennai, Vellore, Lucknow India (SOFACOS)

64% in remission, 6% continuous psychosis, 30% other

61% occupational impairment

PANSS - Positive and Negative Syndrome ScaleGAF - Global Assessment of Function SOFACOS- Study Of Factors Associated With Course and Outcome of Schizophrenia WHODAS, WHO- Disability Assessment Schedule;

The evidence from recent systemic reviews generally support the following conclusion

1. The course of schizophrenia is highly variable both with in patient and between patients.

2. Less then half of patients diagnosed as schizophrenia show substantial clinical improvement after follow-up time averaging 6 years.

3. Examining trend in course and outcome over the past century revealed substantial gains in favorable outcome from the 1920 – 1970 after which time gradient seems to be reversed.

4. Course of descriptors varies as a function of the length of follow-up.

5. On average patient with diagnosis of schizophrenia has the poorest outcome.

6. Course and outcome estimates vary depending on the diagnostic classification used.

7. There is no reliable set of predictors yet identified for course and outcome.

Methodological heterogeneity

• Variation in population from which patient are selected.

• Variation in diagnostic criteria. • Variation in length of illness before entry in to

follow-up.• Variability of attrition rate.

• Variation in methods used to assess course and outcome.

• Variation in the characteristics of the general population.

• Variation in statistical techniques and adjustment of confounding.

• Variation in long term management of schizophrenia.

WHO description of clinical symptoms course and outcome

1. Single psychotic episode followed by complete remission.

2. Single psychotic episode followed by incomplete remission.

3. Two or more psychotic episode with complete remission between episodes.

4. Two or more episodes with incomplete remission between episodes.

5. Continuous (unremitting) chronic psychosis.

International study

• WHO Ten Country Study. (short term)• International Pilot study on Schizophrenia.

(IPSS)• International study of schizophrenia (ISoS)• The study on determinants of outcome of

severe mental disorders.(DOSMeD)

IPSS• IPSS began in 1966 as a large scale cross-

cultural collaborative project carried out simultaneously in nine countries that differ widely in their sociocultural and economic characteristics.

Centre for IPSSCountry Centre

Arthus Denmark

Agra India

Cali Columbia

Ibadan Nigeria

London England

Moscow U.S.S.R.

Taipei China

Washington U.S.A.

Prague Czechoslovakia

IPSS

• In IPSS total 1202 patient has been taken. Out of which 811 received a clinical diagnosis of schizophrenia, 164 affective psychoses, 102 other psychoses.

Method – The IPSS was carried out in three phases, a preliminary phase, an initial evaluation phse and a follow up phase. And all the patient interviewed by using “present state examination”

Outcome in IPSS

• IPSS found that higher proportion of patients in India, Colombia, and Nigeria had better outcomes on most dimensions than patients in developed countries.

• Complete remission of the initial psychiotic episode within 5 years had occurred in as many as 42% of patients in India 33% of patients in Nigeria, whereas the majority of patients in the developed countries had experienced persistent psychotic symptoms.

International study of schizophrenia (ISoS)

• It involves 18 research centers in 14 countries, traced 75% of cases assessed in the earlier WHO studies.

• It includes cohort from IPSS as well as additional cohort from China, Hong Kong, and India.

ISoS summary

• 57% patients had experienced a total of less than 9 months of active psychosis, only 22% had been psychotic for 45-60 months.

Outcome of First EpisodeSchizophrenia 1981

• 15 yr follow-up of FES (Netherlands site DOSMeD study) (Wiersma et al, 1998)• 43% relapsed in 1 yr, 70% by 5 yrs• 11% committed suicide• 26.7% Completely remitted• 50.1 % Partial remission • 11.0% Chronic psychosis • 9/82 chronically psychotic from first episode

Risks for poor recovery

• Period of time spent psychotic in first 2 yrs predicted

• poor outcome• Younger age• Substance abuse• Blunted affect• Loss of social network• Family involvement

Factors influencing the variation in outcome

• Due to additive or interactive effect of genetic difference between populations.

• Ethnopsychiatrist Henry Murphy: proposed four criteria for schizophrenia evoking stress- – A situation demanding action or decision– Complexity or ambiguity of the information supplied to

deal with the task– Unless resolved the situation demanding action or

decision.– The person has no escape route available.

Risk factors for the persistence of schizophrenia

• There is strong evidence that child hood cognitive ability is associated with outcome.

• Lower intelligence has been shown to predict unfavorable clinical and functional outcomes at follow-up.

• Subtle social premorbid adjustment to be associated with less remitting course and poorer functional outcome.

Factors predicting poor outcome Features of the illness• Insidious onset• Long first episode• Previous psychiatric history• Negative symptoms• Younger age at onsetFeatures of the patient• Male• Single, separated, widowed, or divorced• Poor psychosexual adjustment• Abnormal previous personality• Poor employment record• Social isolation• Poor compliance

Natural course of schizophrenia before the neuroleptic era

• Study from urban communities in Scotland and India (padmavati et al. 1998) and rural community in China.

• Outcome of these sample were hetrogeneous but except for larger proportion of Chinese patients having marked psychotic symptoms. They did not differ much from the outcome from the treated group.

Variation in the outcome in schizophrenia

• Systemic investigation in to the course and outcome of schizophrenia were initiated by Kraepelin.

• In a historical study of 70 Swedish patients with first admission in 1925, life time records were retrieved and rediagnosed in accordance with DSM-III. None of these patients received neuroleptics. The final outcome was rated as good in 33%, as profoundly deteriorated in 43%, and as intermediate in 24%.

Secular trend In outcome of schizophrenia

• A meta-analysis of 320 outcome studies on schizophrenia published between 1895 to 1992, which comprise a total of 51,800 subjects.

• Overall about 40% of the patients have been described as improvement after an average length of follow-up 5.6 years.

• There was a significant increased in the rate of improvement during 1956-1985 compared to 1895-1955, clearly related to introduction of neuroleptic treatment.

Cognitive dysfunction inschizophrenia

• Cognitive dysfunction in areas of:– Attention and concentration– Memory– Planning and executive functions • Important in the determination of long term

outcome and social functioning (Green, 1996; Green et al, 2000)

• Cognitive remediation strategies

Relationship of Neurocognitive Impairment to Functioning

• The three types of functional outcome that most studies of neurocognitive deficits have examined are community (social and occupational) outcome, the ability to solve simulations of interpersonal interactions, and success in psychosocial rehabilitation programs.

• A meta-analysis of 26 randomized clinical trials involving a total of 1,151 patients concluded that neurocognitive remediation produces moderate improvements in neurocognitive performance and, when combined with psychiatric rehabilitation, also improves functional outcomes

• Working memory has been described by various authors as a core component of the neurocognitive impairment in schizophrenia and is related to functional outcomes such as employment status and job tenure

Role of imaging in outcome

• Poorer outcome was associated with post onset brain changes in patients diagnosed with a first-episode schizophrenia

• more pronounced brain changes appear to be associated with poor outcome, more negative symptoms, and poor performance on neurocognitive measures, although the latter are more equivocal.

Prognostic factor Good prognosis Poor prognosis

Late age of onset Young onset

Obvious precipitating factors No precipitating factors

Acute onset Insidious onset

Good premorbid, social, sexual and work study

Poor premorbid, social, sexual, and work history

Mood disorder symptoms Withdrawn, autistic behavior

Married Single, divorced, or widowed

Family history of mood disorder Family history of schizophrenia

Good support system Poor support system

Positive symptoms Negative symptoms

Neurological sign and symptoms

H/O perinatal trauma

No remission in 3 years , many relapses

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