"It is proposed that if Social Workers want their knowledge of psychotropic drugs to be taken seriously, then they should consciously develop their own critical appraisals of these drugs, their development, their uses and misuses by the numerous actors involved in the life cycle of drugs, and the scientific, historical, ideological, cultural, and political matrices which determine who uses (and prescribed) which drugs and why" (Cohen, 2002).
First-Generation Antipsychotics
Psychopharmalogical treatment for schizophrenia began in the 1950's and 1960's with neuroleptics (antipsychotics), and are referred to as "first-generation" antipsychotics (aka., typical, conventional, classical). Traditional drugs include: chlorpromazine, thioridizine, and haloperidol. These medications are effective primarily for positive symptoms (hallucinations, psychosis).
By the 1980's, the use of first-generation drugs began to decrease due to significant patient side effects such as acute and chronic movement disorders (extrapyramidal symptoms), which became irreversible in long-term treatment.
Second-Generation Antipsychotics
By 1990, clozapine became the initial and most popular drug used by physicians, in treating a broader level of symptoms with less side effects. The effectiveness of clozapine began the development of an array of "Second-generation" (atypical) agents including: Risperdol, Zyprexa, Seroquel, and Geodon.
Science is continually researching 'best treatment' approaches regarding the psychopharmacology of schizophrenia. There is an increasing amount of evidence to support the effectiveness of second-generation drug treatment within the psychosocial treatment context. Rosenheck, et al., (1998), found that treatment with atypical agents promoted compliance and participation in psychosocial programs. This supports that effective drug treatment can work synergistically with psychosocial treatment in achieving life goals. Because atypical agents work more effectively on negative symptoms i.e., anxiousness and depression, they seem to facilitate psychosocial treatment participation.
The National Institute of Mental Health (NIMH) supported Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE Project). The CATIE Project is the first to study schizophrenia patient responses, using all of the second-generation drugs.
The "goals of the CATIE Project" (Lieberman and Stroup, 2003), are to determine: 1) if second-generation drugs are superior to first generation drugs, 2) how the second-generation drugs compare with each other, and 3) the comparative effectiveness of a representative conventional antipsychotic and the different atypical antipsychotic medications in a broad sample of patients needing treatment for chronic schizophrenia.
Clinical trials have found thus far, that Clozapine has possible severe side effects, such as loss of white blood cells that fight infection. This requires patients to have frequent blood tests. The newer atypical drugs such as Risperdal, Seroquel, and Zyprexa appear to be much safer with less observed side effects.
(Marder, et al., 2003) provide supportive evidence that a second-generation drug (risperidone) when compared to a low dose of a conventional drug (haloperidol) result in fewer tremor side effects, diminished depression and anxiety symptoms, and improved social adjustment.
Study 1 Description:
Objective- To study long-term maintenance treatment, symtoms and side-effects of second-generation vs. conventional antipsychotics.
Method- Longitudinal-2 year, randomized, double-blind study, n=63, between 18-60 yrs.of age, with DSM IV schizophrenia diagnosis. Base-line assessment included clinical psychopathology, side effects, social adjustment, and subjective response measurement scales. Subjects also received haloperidol (8mg) during baseline period. Subject were randomly assigned to either risperidone or haloperidol after base-line. All subjects participated in skills training education (medication management, symptom self-management, social problem-solving) during the first 15 months of the study. One-half of subjects were randomly assigned to additional Amplified Skills Training (i.e.,visiting the pharmacy, learning to use public transportation, getting a library card) (Marder, et al., 2003).
Analysis- Continuous variables were analized using general mixed model analysis of covariance. Repeated point measures were performed at base-line, at 26 weeks, at 52 weeks, at 74 weeks, and at 104 weeks. Effects measured were medication group and time ( and interaction). Analysis of time to dropout, exacerbation of symptoms, etc. was performed using the Kaplan Meier method (Marder, et al., 2003).
Results- Risperidone was associated with less depressive and anxiety symptoms than haloperidol (reliable and consistent with previous findings comparing atypical and typical antipsychotics). Haloperidol and risperidone were both effective in minimizing positive and negative symptoms and in preventing relapse. However, risperidone was associated with less tremor and it is interprested that drug effects on level of mood and extrapyramidal (body movement) side effects may be related.
Participants given risperidone with enhanced skills training measured the highest proportion in adherence to both treatments, showing a significant difference after the first 13 weeks of the study and remaining steady. Participants treated with haloperidol and standard skills training were most compliant for approximately the first 5 weeks, and then exhibited a significant steady decline (Marder et al., 2003).
(Lieberman, et al., 2003) also provide supportive evidence that atypical antipsychotic treated subjects experience significantly less symptom severity than those treated with a conventional antipsychotic (the current article focuses on treating first-episode psychosis, treatment, and symptoms during the first 12 weeks only, of a 104 week study).
Study 2 Description:
Objective- To compare acute and long-term effects of atypical and conventional drug treatments in persons with first-episode psychosis who met criteria for schizophrenia or another psychotic disorder.
Method- Subjects selected for the study (n=263) received treatment as inpatient, outpatient, or emergency services for pscyhotic symptoms, and represented a population within 14 medical centers located throughout North America and Western Europe. Subjects were between ages16-40, had onset of psychotic symptoms prior to age 35, and met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Scales used in assessment included the Structured Clinical Interview and the Positive and Negative Symptoms Scale.
Patients participated in a washout period of 2-14 days (discontinued meds depending on clinical status) as baseline measure. Patients were randomly assigned (double-blind) to either olanzapine or haloperidol during a 12 week acute treatment phase. Initial doses were lowest effective dose for six weeks and then changed in range during the second 6 weeks, allowing the least effective dose while maintaining active treatment.
Assessment measures used in assessing efficacy include the Montgomery Asberg Depression Rating Scale, Clinical Global Impressions, and Positive and Negative Syndrome Scale. Measures and Scales used in assessing safety include Thesaurus for Adverse Reaction terms (COSTART), Simpson-Angus Rating Scale, the Abnormal Involuntary Movement Scale, and the Barnes Rating Scale for Drug-Induced Akathisia (Lieberman et al., 2003).
Analysis- Traditional last-observation-carried-forward ANOVA model, within group t-tests, Fisher's exact and chi-square tests (Lieberman et al., 2003).
Results- Both drug treaments produces significant reductions in symptoms. Olanzapine treated showed greater reduction in symptoms and rates of change using the Montgomery Asberg Depression Rating Scale and the Positive and Negative Syndrome Scale. The last-observation-carried-forward method showed no significant differences for efficacy between both treatment groups, yet found significant reductions in symptoms for both olanzapine and haloperidol.
The Simpson-Angus Rating Scale and Barnes Rating Scale showed significant between-treatment differences in extrapyramidal side effects, with more frequency and severity in the haloperidol group. Haloperidol was associated with greater increase in prolactin.
More olanzopine patients were retained in the study, suggesting that atypical antipsychotics can be associated with long-term adherence.
Weight gain appears to be associated with olanzapine (Lieberman, et al., 2003).
