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Asist. Univ. Dr. Cojocaru Adriana – Președinte SNPCAR


COMPARATIVE STUDY OF TYPICAL ANTIPSYCHOTICS VERSUS ATYPICALANTIPSYCHOTICS CONSIDERING COST/ BENEFIT RATIO IN CHILDREN AND ADOLESCENTS WITH PSYCHOSES

Off , Vol.: 2013,

Autor: Raluca Grozăvescu
Distribuie pe:

Psychotic disorders with onset in childhood or adolescence, as well as those with adult onset, are major mental disorders and the early onset leads to greater severity and very high costs. Also, longitudinal studies conducted in patients with psychoses have shown that their evolution is decisively influenced  by an early correct diagnosis and treatment.

Objective: The main objective was to observe and compare the evolution of patients with  childhood or adolescence onset psychoses in relation to the antipsychotic treatment administered: typical versus atypical.

Method: I conducted an observational clinical study design, for a period of three years,  on 132 patients diagnosed with psychosis, aged 9 to 17 years, with an average age of 14.8 years (standard deviation, SD = 1.944), hospitalized in Clinic of Child and Adolescent Psychiatry of “Prof. Dr.  Al. Obregia” Psychiatry Hospital from Bucharest, who had their first admission in a period of 10 years, namely the period from 1998 to 2007. Diagnosis was made according to ICD 10 and DSM IV criteria, using the psychiatric interview and K-SADS semi-structured interview.

Results and conclusions: We obtained statistically significant differences (p<0,01) between subjects who received atypical antipsychotics, and subjects who received typical antipsychotics (atypical antipsychotics have proved superior), from the point of view of the effect on psychotic symptoms, quality of life, school reintegration, social functioning, the adverse event profile, adherence to treatment.

INTRODUCTION

Psychotic disorders with onset in childhood or adolescence, as well as those with adult onset, are major mental disorders, with a huge negative impact in terms of mental health and social, educational, vocational reintegration and of quality of life for affected people and their families. The early onset of these disorders leads to greater severity and very high costs, as these disorders with chronic evolution have needs for care and treatment spanning virtually the entire life of the patient.

In recent decades, the antipsychotics range has become very wide. Newer medications, called atypical antipsychotics have a much better profile than typical ones in terms of effectiveness for certain symptoms (similar efficacy on positive symptoms and better efficacy for negative symptoms and cognition) but also regarding the occurrence of side effects, with less risk to health and allowing a better recovery and better school, work and social  integration.

In terms of risk / benefit the balance tilts, for children and adolescents as well as for  adults, in favor of atypical antipsychotics (Mc Clellan, 2004, 2009; Lieberman et al, 2005; McEvoy, 2006; Meltzer & Bobo, 2006; Keefe et al, 2007; Lieberman, 2006, 2007; Lewis & Lieberman, 2008; Sikich et al, 2008; Tandon et al, 2007, 2008).

It should be noted however that the price of atypical antipsychotics is – at least for the original drugs – much higher than the price of the typical antipsychotics. In the current economic downturn and considering the difficulties faced by the health system, the analysis of cost / benefit ratio becomes more important  when choosing a treatment.

Through this study, I wanted to answer the question whether the treatment with more expensive, modern medication is justified by its benefits regarding efficacy, safety and tolerability as well as quality of life.

There are studies performed in adults with psychoses showing socio-professional integration significantly better in patients with psychoses who are treated with atypical antipsychotics (Percudani et al, 2004, Tunis et al, 2006).

The general part of the thesis contains five chapters, during which I updated the following aspects: 1.1. the importance of this issue; 1.2. nosographic, epidemiological, etiopathogenic and clinical features and therapeutic principles and evolution of psychoses with onset in childhood or adolescence; 1.3. antipsychotic medications: classic and current definitions, classifications, action on receptors profile, therapeutic and side effects, how to choose a certain treatment and treatment compliance issues; 1.4. quality of life in children and adolescents with psychoses and 1.5. economic and social costs of psychoses with onset in childhood or adolescence.

 

The special part – personal research

Working hypothesis: Longitudinal studies conducted in patients with psychoses have shown that their evolution is decisively influenced  by an early correct diagnosis and treatment (Davies et al, 2003, 2007; McGorry, 2003, 2008, McClellan, 2009, Hirshfield, 2001; Stimmel, 2004). Studies conducted until now showed that classical/typical antipsychotics have effect particularly on positive symptoms and prevent relapses but have no effect on  or even worsen negative symptoms. They do not improve the deterioration process and there are numerous studies showing that it augments the cognitive impairment characteristic of psychotic disorders. Atypical antipsychotics appear to have similar efficacy on positive symptoms  but improve negative symptoms and do not affect or even improve cognition (Stahl, 2008, Mueser, 2006; McClelan, 2009, Baroni, 2009).

This thesis begins from the hypothesis supported by clinical experience and also by studies in the literature that there is a significant difference between the effectiveness of atypical antipsychotics compared with typical, in terms of global functioning, school reintegration and quality of life, which requires choosing atypical antipsychotics as first-line medication in psychoses with onset in childhood or adolescence.

Objectives: The primary objective was to observe and compare the evolution of patients with  childhood or adolescence onset psychoses in relation to the antipsychotic treatment administered: typical versus atypical.

I investigated the response to antipsychotic treatment in terms of efficacy: psychotic symptoms, quality of life, school reintegration, social functioning. Another aspect was that of tolerability reflected by: the adverse event profile, no need to change treatment, adherence to treatment.

Regarding treatment costs, atypical antipsychotics are significantly more expensive than typical antipsychotics. I analyzed the results of typical versus atypical antipsychotic treatment to see if there is a significantly greater therapeutic benefit of atypical antipsychotics to justify higher costs.

I followed up these patients for a period of three years, recording data regarding symptoms severity for each psychotic episode, number and duration of these episodes, duration and quality of remission periods, social and educational reintegration quality and quality of life, in order to see if there are significant differences in their evolution between those who received treatment with typical antipsychotics and those receiving treatment with atypical antipsychotics.

I also followed up the duration of hospitalization during acute episodes, and duration of school break to estimate the additional costs related to the care and education of these patients.

Secondary objectives of the study were to evaluate these patients in terms of family history, personal history of physiological and pathological psychomotor development, family environment and premorbid school route, to investigate whether there are certain factors associated with emergence of psychoses in children and adolescents and to investigate if there are certain factors influencing the evolution of these patients, independent of received treatment.

Material and method

I conducted an observational clinical study design, directed towards a well defined category of patients: children and adolescents diagnosed with psychosis.

Study group: 132 patients diagnosed with psychosis, aged 9 to 17 years, with an average age of 14.8 years (standard deviation, SD = 1.944), hospitalized in Clinic of Child and Adolescent Psychiatry of “Prof. Dr.  Al. Obregia” Psychiatry Hospital from Bucharest, who had their first admission in a period of 10 years, namely the period from 1998 to 2007. Patients were diagnosed with schizophrenia or affective psychosis (bipolar disorder, schizoaffective disorder or unipolar major depression). Diagnosis was made ​​according to ICD 10 and DSM IV criteria, using the psychiatric interview and K-SADS semi-structured interview.

Patients were followed for 3 years, in terms of symptoms, the severity of episodes, the number and duration of relapses, as well as regarding the overall functioning, school integration, networking with age group, the subjective perception of quality of life , adherence to treatment and side effects.

Antipsychotic treatment was prescribed by their treating physician of Child and Adolescent Psychiatry Clinic, patients were registered and followed up for a period of three years. The study was prospective, observational. I did not intervene in treatment prescription, I just collected data on treatment and applied scales and interviews used to assess subjects, at their inclusion in the study and also during the study.

Among the atypical antipsychotics there were used: risperidone (dose range 2-4mg/day), aripiprazole (10-20 mg/day), olanzapine (5-20mg/day) and ziprasidone (40-80mg/day). Among the typical antipsychotics were used: haloperidol (at doses of 5-15mg/day) and zuclopentixolul (30 -50mg/day).

I opted for an observational study primarily for ethical reasons, leaving the choice of treatment up to the treating doctor, so that each patient had the opportunity to receive the medical treatment that his treating doctor  considered to be the most appropriate .

Selection of subjects was made ​​according to the following criteria:

Inclusion criteria: Age between 9 and 17 years (up to 17 years and 11 months, one day less than 18 years) at  psychosis onset; having at least one hospitalization in the Clinic of Child and Adolescent Psychiatry in Psychiatric Hospital “Prof. Al. Obregia” in Bucharest and remained in the Clinic records at least three years; meeting ICD 10 and DSM IV-TR criteria for the diagnosis of psychosis; having an IQ over 50; have received maintenance treatment with typical or atypical antipsychotic drugs.

Exclusion criteria: I excluded patients with moderate and severe mental retardation and those with chronic somatic disease, epilepsy or other neurological disorders and the patients who received combined treatment with typical and atypical antipsychotics  for more than two weeks.

 

Dividing the study group

To study differences between patients treated with atypical antipsychotics and those treated with typical antipsychotics, I divided the study group into two groups, the criterion being the type of antipsychotic treatment received as follows: Group 1 – subjects receiving treatment with atypical antipsychotics (71 patients); Group 2 – subjects were treated with typical antipsychotics (61 patients).

 

Method and Tools

For diagnostic procedure I used semi-structured clinical interview for affective disorders and schizophrenia for school-age children (K-SADS-PL).

To obtain socio-demographic data, personal background and family history and those related to premorbid school route, social and school at 3 years of development of psychotic disorder I used a set of questions that were addressed  to carers. To determine the severity of the disorder in the episode I used the Clinical Global Assessment Scale (CGI), the clinical severity component. I used the Clinical Global Assessment Scale for Children (CGAS) to determine the overall functioning of patients  at different times, according to study design. For quality of life I used self-assessment scale of quality of life, joy and satisfaction for pediatric population (PQ-LES-Q).

 

Description of analyzed variables

In this group which included all enrolled patients and the previously described two groups I  analyzed the following socio-demographic and clinical variables:

  • Age, sex, residence (urban or rural); Family type to which patient belongs: organized, disorganized or institution / foster parent;
  • Family environment: harmony or tension (arguing, violence, alcohol abuse);
  • Socio-economic status of the family: very good and good (at least middle income), low (minimum income) or poor (social assistance for socio – economic reasons);
  • Family history (AHC), where we considered the following categories: 1.not significant, 2. psychosis in one or both parents, 3. psychosis in other relatives, 4. parents’ other  mental illness;
  • Personal history called physiological (APF) – in terms of pregnancy outcome, the following categories: 1.not significant, 2. repeated bleeding during pregnancy and / or threatened abortion, 3. administered drugs during pregnancy, not recommended by doctor;
  • Personal history called physiological (APF) – in terms of suffering at birth: 1. without suffering at birth 2. suffering at birth (APGAR ≤ 8), 3.suffering from birth (APGAR ≤ 8) and prematurity, 4. small for gestational date;
  • Pathological personal antecedents (APP) – mental – other than psychosis 1.not significant, 2. psychiatric disorders  included in anxiety / depression categories, 3.disorders from  ADHD / opposition disorder / conduct disorder category;
  • Pathological personal antecedents (APP) – Somatic: 1.not significant, 2. neonatal infections, jaundice prolonged, convulsions, 3. craniocerebral traumatism, 4.meningitis, encephalitis;
  • DPM (psychomotor development): 1.normal, 2. mental development delay, 3. motor development delay, 4. psychomotor development delay;
  • Intelligence quotient (IQ): 1. IQ greater than or equal to 70, 2. 70
  • Attendance at kindergarten: 1. Attende kindergarten  at least 1 year, 2. did not attend kindergarten;
  • Premorbid school functioning, with the following: 1. Good (good / average teaching without problem behaviors), 2. Poor (poor performance in school, no problem behaviors), 3. Very weak (poor to education and problem behaviors, aggression);
  • Premorbid social functioning, with the following: 1.good, 2. poor (no friends, casual relationships), 3. very poor (social isolation);
  • Type of treatment with antipsychotics, with two categories: 1. Atypical antipsychotics and 2. typical antipsychotics;
  • Number of admissions in three years, the number of days of hospitalization in 3 years (total days of hospitalization); CGI-S score determined at the first episode and afterthree years from onset;
  • Premorbid CGAS score (retrospectively estimated), at the first episode and after 3 years;  PQ-LES-Q score (scale of assessment of quality of life, joy and satisfaction in the pediatric population) after the first episode, the first period of remission and after 3 years;
  • The longest period without psychotic symptoms, with the following categories: 1. over 1 year, 2. 6 months – 1 year, 3. under 6 months 4. no remission;
  • The number of necessary drug changes (whenever it was necessary to change the treatment during this period of 3 years), with the following categories: 1. was not changed, 2. was changed once in 3 years, 3. was changed two times, 4. was changed at least 3 times;
  • Treatment compliance, with the following categories: 1. good 2. average, 3.low. I considered good compliance when treatment was administered systematically, average compliance when some daily doses were missed but not more than once a week and a low compliance when daily doses are missed more frequently than once per week;
  • Reasons for medication change, with the following categories: 1.drug inefficient, 2.Significant or unacceptable side effects, 3.other reasons (social, the product could not be purchased), 4. was not changed;
  • School interruption, with the following categories: 1.less than 3 months, 2. 3 months to 12 months, 3.1 to 3 years (repeated year / years), 4.dropout school;
  • School integration after three years (3 years after the onset of psychosis), with the following categories: 1.had graduated high school / vocational school (or is still in school with a break of less than 1 year), 2. still in school (with a break of more than 1 year), 3. dropout from school;
  • Social functioning after 3 years (at 3 years after the onset of psychosis), the following categories: 1. attending a group of friends, 2. occasional interactions with people in the age group, 3. Isolated;
  • Significant side effects, with the following categories: 1. Weight gain more than 10%, 2. Extrapyramidal effects requiring treatment or changing antipsychotic, 3. Other important effects, 4. No serious side effects.

Statistical data processing was done using several tests, depending on the variables processed:

  1. Student’s t test, for independent samples – used for comparison between the means of quantitative variables, measured on two independent samples;
  2. Mann-Whitney Test (nonparametric variant t of the test for independent samples);
  3. CHI Square Test (CHI SQUARE) – used for tests of homogeneity or independence, to check assumptions as dependence or independence of factors of classification used;
  4. General linear model: a model for analyzing repeated measurements on a variable in different times, for the same sample;
  5. Analysis of variance (ANOVA = Analysis of Variance) – is used for comparing more than two averages of a quantitative variable between independent samples;
  6. Post Hoc Tests (tests between pairs of measurements), to check the results obtained by ANOVA;
  7. Kruskal-Wallis Test (nonparametric version of analysis of variance).

 

Results and discussion

A.1.Socio-demographic variables, medical, social and school functioning history

I did not obtain statistically significant differences between group 1 and group 2 regarding age (p = 0.930), gender (p = 0.477), residence (p = 0.542), family organization (p = 0.0781), family history (AHC) (p = 0.349), personal history called physiological (APF) related to pregnancy evolution (p = 0.152) and those of suffering from birth and gestational age (p = 0.915), pathological personal antecedents (APP) – psychiatric (other than psychosis) (p = 0.11), pathological personal antecedents (APP) – somatic (p = 0.417), psychomotor development (DPM), (p = 0.367), intelligence quotient (IQ), (p = 0.61), premorbid social functioning (p = 0.144). These results show that the two groups were similar in these respects.

I obtained statistically significant differences between group 1 and group 2 regarding the family environment (p = 0.001) and family socioeconomic status (p <0.01). Given these differences we calculated correlations between each of the two variables and other variables and the results were not statistically significant (I presented these results in section “Correlations between variables”). This shows that these differences between the two groups did not significantly affect the results.

A.2. Clinical Quantitative Variables

a) Scores of severity of disorder, estimated at onset and 3 years after onset, the overall functioning and quality of life.

CGI-S comparative analysis: Average score of clinical severity CGI-S in the first episode was similar for both groups: 5.72 (SD = 0.778, ES = 0.092) for group 1 and 5.74 (SD = 0.751, ES = 0.096) for group 2, with no significant difference in clinical severity scores of the first episode between the two groups (p = 0.885), indicating that in terms of severity of psychotic symptoms in the first episode group 1 and group 2 were similar.

In terms of clinical severity scores at 3 years, CGI-S at 3 years, there was a statistically significant difference (p <0.0001) between the two groups, the average CGI-S obtained for the three years were: 2 , 10 (SD = 0.720, ES = 0.085) respectively for group 1 and 2.54 (SD = 0.673, ES = 0.086) in group 2 (SD = standard deviation, ES = standard average error).

In terms of clinical severity scores at 3 years, CGI-S at 3 years, there was a statistically significant difference (p <0.0001) between the two groups, the average CGI-S obtained for the three years were: 2 , 10 (SD = 0.720, ES = 0.085) respectively for group 1 and 2.54 (SD = 0.673, ES = 0.086) in group 2 (SD = standard deviation, ES = standard average error).

Comparative analysis of CGAS for the two groups (group 1 and group 2): global functioning scores were also similar, for both the premorbid and the first episode: premorbid CGAS had an average of 86.92 (SD = 7.926, ES = 0.941) for group 1 respectively 83.79 (SD = 6.661, ES = 0.853) for group 2 and CGAS in first episode averaged 19.51 (SD = 9.361, ES = 1.111) for group 1 and that 19.87 (SD = 8.595, ES = 1.101) for group 2, which means that both in terms of global functioning and of premorbid overall functioning in the first episode the groups were similar.

There were statistically significant differences (p <0.0001) between global functioning scores obtained at 3 years after onset: CGAS at 3 years after onset for group 1 (patients who received atypical antipsychotics) had an average of 77, 17 (SD = 10.159, ES = 1.206) and for group 2 had an average of 70.11 (SD = 8.021, ES = 1.035).

Comparative analysis of results on quality of life: Differences in results from scales to assess quality of life (PQ-LES-Q) were not statistically significant for the values ​​obtained after the first episode, but were statistically significant (p = 0.001) for those obtained after 3 years of development of psychosis (scores significantly higher in patients receiving atypical antipsychotics): average PQ-LES-Q scores after the first episode was 34.10 (SD = 6.057, ES = 0.719) for group 1 and 33, 89 (SD = 4.820, ES = 0.617) for group 2, and average PQ-LES-Q scores after 3 years of development was 48.07 (SD = 6.149, ES = 0.730) for group 1 and 44.43 respectively (SD = 5.806, ES = 0.743) in group 2.

b) The number of hospitalizations required on a period of 3 years after onset. Number of days of hospitalization: number of hospitalizations and number of days of hospitalization reflects periods of decompensation (acute psychotic episodes) or crisis, which forced hospitalization. During the three years analyzed, the group of patients who received atypical antipsychotics – group 1– I found an average of 3.00 admissions (SD = 1.242, ES = 0.147) and an average of 54.45 days of hospitalization (SD = 28.046, ES = 3.32) and in group of patients receiving typical antipsychotics – group 2 – I found an average of 3.80 admissions (SD = 1.631, ES = .209) and averaged 83.49 inpatient days (SD = 38.198; ES = 4.891).

Patients receiving atypical antipsychotics had fewer hospital admissions and fewer days of hospitalization  during the study and these differences were statistically significant (p = 0.002 for number of hospitalizations and p <0.0001 for number of days of hospitalization during the three years studied).

A.3. Clinical Qualitative Variables

1) Duration of remission – the longest period without psychotic symptoms

In patients of group 1 (those who received treatment with atypical antipsychotics), the longest period without psychotic symptoms was over 1 year in most subjects: i.e. 67.6%, from 6 months to 1 year to 19.7 %, less than 6 months to 8.5% and 4.2% there was no remission. In patients of group 2 (those who received treatment with typical antipsychotics), the longest period without psychotic symptoms was between 6 months and one year in most patients: 55.7%, over 1 year: 18%, under 6 months: 13.1% and in 8.3% there was no remission. Differences between the two patient groups (two groups) were highly statistically significant (p <0.0001).

2) Effectiveness and tolerability: the need of changing treatment

For patients in group 1 (those who received treatment with atypical antipsychotics) in most subjects, i.e. 69.0% it was not necessary to change treatment; in 19.7% the treatment was changed once during the 3 years study, in 9.9% was changed twice and only in 1.4% changing the antipsychotic was required 3 times.

In patients of group 2 (those who received treatment with typical antipsychotics) in 34.4% was not necessary to change treatment; in most subjects, i.e. 41.0%, treatment was changed once in 3 years study; in 21.3% was changed twice and only in 2.3% it was required to change the antipsychotic medication 3 times.

Differences between the two groups were statistically significant (p = 0.001). The need to change therapy may be an indicator for both efficacy and tolerability of treatment and the reasons for changing treatment also provide a qualitative analysis relevant to efficacy and tolerability.

3) Reasons for treatment change
In patients of group 1: in most subjects, i.e. 69.0% it was not necessary to change treatment; in 11.3% the treatment was changed because it was ineffective and in 8.5% was changed due to side effects; in 11.3% the treatment was changed for other reasons.

In patients of group 2: in most subjects, i.e. 36.1%, treatment was changed because of side effects, in 14.8% the treatment was changed because it was ineffective, in 14.8%, treatment changed for other reasons, and in 34.4% was not necessary to change treatment.

The treatment with atypical antipsychotics was superior to that with typical antipsychotics in terms of the need to change treatment, the differences between the two groups being statistically significant (p = 0.001 for number of changes in treatment and p <0.0001 in terms of reasons change of treatment).

4) Compliance to treatment
Compliance to treatment was significantly (p <0.0001) greater in patients treated with atypical antipsychotics.

Subjects in group 1 had mostly, i.e. 83.1%, a good compliance; 14.1% had an average compliance and 2.8% had a poor compliance to treatment. Subjects in group 2 had mostly an average compliance, i.e. 55.7%, while 27.9% had good compliance, and 16.4% had poor compliance.

5) Tolerability – major side effects
In group 1, 22.5% of subjects had a weight gain of over 10% of the weight at onset during the 3 years, 2.8% had significant extrapyramidal effects, which required treatment or stopping of antipsychotic and most 74 , 6% had no significant side effects.

In group 2, only 3.3% had weight gain more than 10%, over half (54.10%) had significant extrapyramidal effects, requiring treatment or changing antipsychotic, 19.7% had other important adverse effects such as difficulty in concentrating, drowsiness, and only 23% had no significant adverse effects.

Treatment with atypical antipsychotics was associated with no significant adverse effects, with a significantly better tolerability profile, with the exception of weight gain while typical antipsychotic treatment was correlated with the presence of significant extrapyramidal effects. Between the two groups there was a statistically significant difference (p <0.001) in terms of adverse effects.

4. Evolution in terms of social and scholar functioning

1) Interruption of school
An important indicator of the extended effectiveness of treatment is stopping school. I analyzed the total duration of school stopping during the three years.

There were statistically significant differences (p <0.0001) between group 1 and group 2. Treatment with atypical antipsychotics was associated with stopping school for less than three months, while treatment with typical antipsychotics was associated with stopping school for a period of more than one scholar year, meaning patients repeated at least one academic year due to medical reasons, and the dropout rate was lower in subjects who received treatment with atypical antipsychotics (11.3% for atypical to 26.2% for typical).

In group 1, 47.9% of subjects had a school break for less than 3 months, 23.9% had a school break for more than three months but less than a year without repeating the academic year, 16.9% had a school break of between 1 and 3 years with repetition of at least one school year and 11.3% dropped out of school.

In group 2, 4.9% of subjects had a school break for less than 3 months, 14.8% had a school break for more than three months but less than a year without repeating the academic year, 54.1% had a school break of between 1 and 3 years with repetition of at least one academic year and 26.2% dropped out of school.

These results further emphasize that treatment with typical antipsychotics may have significantly worse results in terms of school integration and even if it is much cheaper it involves some additional indirect social costs in terms of patient school enrollment receiving this type of treatment compared with school enrollment of patients receiving atypical antipsychotics.

Although there were no significant differences in the scores of disease severity between the two groups, there were highly statistically significant (p <0.0001) differences in terms of school dropout.

2) The scholar situation – school integration after 3 years of development
The results obtained from comparative analysis of the two groups for the variable “school integration after three years” reinforce the results for the variable “school dropout”. Thus, there were significant statistic differences (p <0.0001) too between the two groups in terms of school integration after three years after the onset of psychosis, the treatment with atypical antipsychotics correlated with the graduation of high school or vocational school, with disruptions less than a year, i.e. without ever losing a school year, while the treatment with typical antipsychotics correlated with remaining in community but with disruptions for more than a year.

School integration after three years in group 1 was as follows: 70.4% of subjects had graduated high school or vocational school or were still in school, with an interruption of less than one year without repeating school years at study completion, 18.3% were still in school but repeated at least one school year and 11.3% dropped out.

School integration after 3 years in group 2 was as follows: 14.8% of subjects had completed high school or vocational school or were still in school, with an interruption of less than one year without repeating school years at study completion, 66.8% were still in school but repeated at least one school year and 26.2% dropped out.

3) Social functioning after 3 years of evolution: group 1 had in terms of social functioning after 3 years 54.9% variant 1 ( a group of friends with whom they hang-out); 32.4% had variant 2 (occasional interactions with same age people) and variant 3 had 12.7% (social isolation). Group 2 was in terms of social functioning after 3 years 6.6% variant 1 (a group of friends with whom they hang-out) 63.9% variant 2 (occasional interactions with same age people) and 29 5% version 3 (social isolation).

Thus, treatment with atypical antipsychotics was associated with maintaining a good social functioning after 3 years, most patients attending a group of friends (54.9%) while treatment with typical antipsychotics was associated with poorer social functioning, with occasional interactions with same age people (63.9%).

Analysis of correlations between the variables studied

I analyzed for the entire group (the group consisting of all enrolled subjects) the correlations between values of several variables pairs, namely: CGI-S in the first episode with CGI-S at 3 years; premorbid CGAS with the first episode CGAS; premorbid CGAS with CGAS at 3 years; CGAS the first episode with CGAS at 3 years; PQ-LES-Q score after the first episode with PQ-LES-Q score at 3 years.

I made this correlation analysis in order to observe: 1. If the forms of disease with more severe symptoms during the first episode are correlated with the persistence of severe symptoms, i.e. a more severe evolution (first pair of variables); 2. If the overall premorbid functioning is correlated with global functioning during the acute episode (second pair of variables); 3. If the overall premorbid functioning correlates with long-term global functioning, i.e. after 3 years in our study (third pair of variables); 4. If the overall functioning during the first episode is correlated with long-term global functioning, i.e. after 3 years in our study (fourth pair of variables); 5. If the score for quality of life achieved after the first episode is correlated with the same score obtained after three years of development (fifth pair of variables).

Applying the correlation coefficient r of Pearson we obtained results showing that: the first episode scores were higher than their pairs obtained from 3 years of evolution (CGI-S analysis); a better long-term prognosis considering global functioning in patients with better global functioning in premorbid period and the overall functioning of the patient in the first episode does not correlate with its overall functioning at 3 years of evolution (CGAS analysis); patients with a better quality of life score after the first psychotic episode will have a better score after three years of evolution (i.e. the values ​​obtained at the scale quality of life after first psychotic episode are correlated with those obtained at three years from onset).

These results were confirmed by Student’s t test. To check the results obtained with the correlation coefficient (r) of Pearson and Student’s t test, I applied nonparametric tests, which gave concordant results.

Therefore, we obtained statistically significant correlations for all tests applied, confirming empirical observations about this group of antipsychotics.

 

Conclusions

  1. Patients receiving atypical antipsychotics had fewer hospital admissions and totaled fewer days of hospitalization during the study.
  2. Patients receiving atypical antipsychotics have after 3 years of evolution: a. an average of the scores of clinical severity (CGI-S to 3 years) less than those receiving typical antipsychotics (group 2), b. a global functioning better than those in group 2, c. an obviously better quality of life than those in group 2, and d. a better social functioning.
  3. In terms of remission’s duration the treatment with atypical antipsychotics was vastly superior to the treatment with typical antipsychotics and the need to change therapy occurred less frequently and at a much lower percentage of cases.
  4. Adherence to treatment was significantly (p <0.0001) higher in patients treated with atypical antipsychotics, especially because the side effects were much reduced – especially the extrapyramidal (except weight gain).
  5. Treatment with atypical antipsychotics was associated with stopping school for less than three months, while treatment with typical antipsychotics was associated with stopping school for a period of more than one school year, thus repeating at least one school year for medical reasons. Also, the drop out rate was much lower after a period of 3 years development in the first group.

There were significant differences between the two groups also in terms of school integration after three years from the onset of psychosis, treatment with atypical antipsychotics correlates with the graduation of high school or vocational schools, with disruption for less than a year without losing an academic year while treatment with typical antipsychotics was associated with maintenance in the community but with breaks for more than a year. School dropout was more common in patients treated with typical antipsychotics.

In terms of social functioning, treatment with atypical antipsychotics was associated with better social functioning at 3 years, majority of patients having a group of friends which they attended (54.9%) whilst treatment with typical antipsychotics was associated with a worse social functioning, with occasional interactions with people in the same age group (63.9%), with p <0.0001.
There were no significant correlations between scores on scales of self-assessment of quality of life at 3 years of evolution (PQ-LES-Q) and socioeconomic status, nor between these scores and family environment, but there were correlations between scores on scales assessing the quality of life and type of treatment, treatment with atypical antipsychotics leading to better scores. This shows that antipsychotic treatment significantly affected in the long term the quality of life in patients with psychoses, while other factors such as socioeconomic status and family environment statistically did not significantly affect the quality of life, although we would have expected them to be at least as important. This is an additional argument for the importance of choosing an appropriate pharmacological therapy in psychoses.

Interruption of school (temporary or permanent), impaired school performance and relationships with age group are issues that precede and accompany the disorder and significantly affect the whole life of the child or adolescent with psychosis. I believe that remaining in the community, school graduation, and school performance can be objective long term indicators, both for assessing quality of life and for evaluating treatment efficacy in this age group. Other objective, easy to quantify “treatment performance” indicators could be the number of days of hospitalization, the number of days / months / years of school stopping.

This thesis supports choosing atypical antipsychotics as a more effective and better tolerated treatment of psychoses with childhood or adolescence onset. Even if it appears to be more expensive in the short term, it will be less expensive in the long term ensuring a superior social, scholar and later professional integration together with a better quality of life.

Treatment with atypical antipsychotics, although it is apparently more expensive in the short term will be less expensive in the long term because it provides fewer relapses and a better social, school and vocational reintegration as well as a better quality of life.
Psychosis with onset in childhood or adolescence are severe disorders, devastating, with chronic evolution. Both schizophrenia and affective psychoses can be controlled but not cured. However, the atypical antipsychotics profoundly changed the outcome of these patients and professional attitude. Although treatment and de-stigmatization issues are not fully resolved, we can speak today of recovery, rehabilitation and socio-professional integration in patients with psychosis

 

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