Pharmacotherapy for Schizophrenia

 

~~~~~~~~~~

 

Survey of Service Users and Staff

undertaken by Dr. Peter Berger,  BA., MA., Ed.D. in response to

the NICE appraisal  of newer (atypical) antipsychotic drugs

in the treatment of schizophrenia

 

 

Table of Contents

Abstract

 

 

Section 1

Introduction

3

Section 2

Executive Summary and recommendations

4

Section 3

Review of Selected Literature

6

Section 3

Survey methodology

11

Section 4

Survey findings

16

Section 5

Conclusions

24

Appendix A

Survey Questionnaire

28

Appendix B

Selected charts of findings

30

Appendix C

References

33

 

                                                                        Abstract

 

This submission offers MACA’s view of how people receiving medications actually are doing now that many of our people are receiving the new atypical antipsychotic medications.  This study aims to explain the impact of these new medications on service users.

MACA uses it’s network of mental health projects to ascertain how much progress has been made in offering the new medications to people who have been taking traditional “typical” antipsychotic medications for many years.   We wanted to see how people were doing with their medications, whether old typical agents, or new atypical medicines.

We investigated the question of whether prescribing practice differs among projects working with different consultants and health care trusts.  we wanted to ascertain whether people with mental health problems are being treated equally; or whether instead there are inequities, with some receiving more or less effective treatments, depending on where they live, and which psychiatric service is prescribing for them.

To achieve our research objective we developed a questionnaire that offers the researchers a full audit of all medications being taken by MACA service users.  The questionnaire is aimed at answering several working hypotheses.

 

 

We expected to discover if:

 1.

 

People changing to atypical antipsychotic medication from old antipsychotic medications will be observed to have improved quality of life, improved mental health, and less medication side effects than people retained on traditional medications.  

2.

  

People changing to atypical antipsychotic medication from old antipsychotic medications will experience improved quality of life, improved mental health, and less medication side effects than people retained on traditional medications.  

3.

Observers will perceive more improvement than service users will experience.

4.

Prescribing practice significantly differs among the different projects by different prescribing practitioners.

 

Our report cites studies that illustrate the research basis supporting this particular study.  We show evidence that the current study is based on sound prior investigations.

 

This study used methodology that allowed comparison of prescriptions on an equal basis.  Thus, no matter the substance, data is dose-sensitive.  Each subject’s prescription was scored for total daily typical antipsychotic dose, and total daily atypical antipsychotic dose.  A standard unit of medication equivalent to 500 mg daily of chlorpromazine was used to compare equally every antipsychotic medication currently approved in the UK.  The assumed equivalencies are reported.   Data about side effect medications, polypharmacy, and use of antidepressants and anxiolytics was also gathered.  

We were able to gain significant data related to many mental health service users’ views about their current medications.  We gained a second opinion, by asking staff member who knew subjects well to offer evaluations of progress since medication changes.  We also were able to gain a view of prescribing practice in various regions and by different health providers throughout the country.   

Data was gathered from 189 service users representing 31 MACA schemes.

 

Our findings indicate that, for people suffering from schizophrenia, those receiving the new atypical anti-psychotic medications experience statistically significant improvement in mental health, perceive a better quality of life, and experience significantly less side effects than people left on the old typical anti-psychotic medications.  These outcomes were highly correlated to close observers, who's reports parallel the service user's views.

 

Our observations point to an optimistic finding that clinical and scientific evidence AND medical-economic models harmonise with our broader-based observations including assessments of clinical efficacy, side effect profiles, quality of life, and cost-benefit analyses, all pointing in the same direction; away from the old medications with their side effects (and side effect medications) and devastating adverse health effects, toward an age in which pharmacotherapy for schizophrenia includes only the most efficacious, least toxic preparations.  We observe that clinical outcomes, moral-ethical imperatives and medico-economical views converge.

 

                       

Section 1

Introduction

 

“Comparing to various meds inc. depixol, haldol, stelazine, largactil, olonzapine has proved better with no side effects. It also quietens the voices to a minimum, still allowing you to function "Normally". As opposed to depixol, which caused side effects like impotence, shakes, and paranoia. The only disadvantage with Olanzapine, due to the high dose I’m on, its meant considerable weight gain.”

 “I have noticed that it [Olanzapine] has worked well in bringing down the symptoms of depression, which I have been trying to cope with for some time. It is one of the better drugs I’ve tried as it is important to note that I’ve noticed very little side-effects….. benefits can be seen. I have greatly improved and I’m sure the medication has helped my condition.”

Two MACA service users, Shropshire

 

This submission offers evidence of how people receiving medications actually are doing now that many service users are receiving new atypical antipsychotic medications.  This study aims to explain the impact of these new medications on service users.

MACA’s network of mental health projects was used to ascertain how much progress has been made in offering the new medications to people who have been taking traditional “typical” antipsychotic medications for many years. (A chart showing the gender and age of service users in the 31 projects surveyed is at Appendix B.)  We recognise that long-term exposure to the typical agents carries a risk of permanent damage from tardive dyskinesia.  We are hopeful that those individuals most exposed to that risk will be offered the chance for better medications that  minimise any damage already done.  We investigate the question of whether prescribing practice differs among projects working with different consultants and health care trusts.  The question comes down to asking whether people with mental health problems are being treated equally; or whether there are inequalities, with some receiving more or less effective treatments, depending on where they live, and which psychiatric service is prescribing for them.

To achieve our research objective we developed a questionnaire that offers the researchers a full audit of all medications being taken by MACA service users.  The questionnaire is aimed at answering several working hypotheses.

Our questionnaire focuses on each service user’s most recent change in main antipsychotic medication.  We will be able to ascertain exactly what recent changes are taking place at the grass roots. 

Our  hypotheses are:

 

 

1.

People changing to atypical antipsychotic medication from old antipsychotic medications will be observed to have improved quality of life, improved mental health, and less medication side effects than people retained on traditional medications.

 

2.

People changing to atypical antipsychotic medication from old antipsychotic medications will experience improved quality of life, improved mental health, and less medication side effects than people retained on traditional medications.

 

3.

Observers will perceive more improvement than service users will experience.

 

4.

Prescribing practice significantly differs among the different projects by different prescribing practitioners.

 

 

Specific working hypotheses are stated in Section 3, which explains the methodology used in this study.  It is important to recognise the impact on quality of life and side effects as well as symptom reduction efficiency. We believe a comprehensive appraisal should bear in mind not just the cost-effectiveness of the medication under consideration but the cost of less effective prescribing practices which lead to additional costs in a patient’s care elsewhere.

 

We also believe that users of mental health services should be offered the widest choice of medication appropriate to their needs, along with the fullest information about that medication. In a nutshell, patients with severe and enduring mental illness have a right to the most modern treatment available.

 

Section 2

 

Executive Summary

 

This submission offers evidence on the impact of “typical” and new “atypical” antipsychotic medications on service users.

Staff and service users from 31 services provided by MACA were asked questions to ascertain how much progress has been made in offering the new medications to people who have been taking traditional typical antipsychotic medications for many years, and how they affected quality of life, mental health and side effects.

We investigate the question of whether prescribing practice differs among projects working with different consultants and health care trusts. We ask whether people with mental health problems are being treated equally, or whether there are inequalities, with some receiving more or less effective treatments depending on where they live, and which psychiatric service is prescribing for them.

 

Review of literature

 

A review of selected literature suggests that clinical and scientific evidence harmonises with our broader-based observations including assessments of clinical efficacy, side effect profiles, quality of life, and cost-benefit analyses, all pointing in the same direction - away from the old medications with their side effects (and side effect medications) and potentially devastating adverse health effects, toward an age in which pharmacotherapy for schizophrenia includes only the most efficacious preparations

 

Methodology

 

We felt that our best contribution would derive from the wealth of direct information we could gain by looking at how our numerous mental health service users are actually prescribed for, and what differences, if any, we could document.  We wanted to examine what pharmacological approaches are in practice with service users, and how service users are responding to the psychiatric (pharmacological) treatment they are currently receiving.

 Questionnaire

We developed a questionnaire that offers the researchers a full audit of all medications being taken by service users, and focuses on each service user’s most recent change in main antipsychotic medication.  Responses were sought from

service users - tenants in residential care homes, and community based and supported homes, and service users of whom we have experience or knowledge of their pharmacotherapy

observers - a near relative or a member of the MACA service’s care staff who has known the service user for a long enough time to make informed observations. Often this will be the key worker.

Primarily, the questionnaire seeks findings on

 

            Observed change in quality of life

            Observed change in mental health

            Observed change in side effects

            User-perceived change in quality of life

            User-perceived change in mental health

            User-perceived change in side effects.

 

We undertook our investigation of these six constructs.  On the basis of our findings we are able to confidently make the following recommendations.

 

                                                                        Recomendations

 

1.         On the evidence of this study, the newer atypical antipsychotic medications produce a better quality of life and improved mental health compared to the older typical antipsychotic medications.  We recommend that atypical antipsychotics should be considered the first line treatment of choice, with the typical antipsychotics only being considered when the former have demonstrably failed.

 

2.         There is a large variation in prescribing practice evidenced in this study. We recommend the drawing up of clear national guidance on standards of prescribing practice, including frequency of review. We recommend that a full review of prescribing to service users on long-term medication should take place at least once a year.

 

3.         The perception by services users that their quality of life diminished as the use of anti-side effect medications increased strengthens the recommendation that the newer atypical drugs should be the treatment of first choice, with typical antipsychotics only being used when the former have demonstrably failed.

 

4.         The study raises questions about the continued widespread use of depot injections given the findings that increasing use of these leads to a diminished quality of life and poorer mental health.  We recommend that the whole rationale for this method of drug administration is reviewed.

 

5.         Increasing use of polypharmacy leads to a diminished quality of life and increased side effects.  We recommend tighter regulation and review of this prescribing practice.

 

6.         In any national guidelines developed, we recommend that particular attention is paid to the monitoring and review of prescribing practice for older, former long-stay patients.  On the evidence of this survey, they are not being given equitable access to the newer atypical antipsychotic drugs.

 

7.         We recommend that the provision of full information on the different types of medication available should be made a clear requirement in any prescribing situation.  The information needs to be in a form that is readily accessible to and understood by the recipient.

 

1.                   We recommend that the improvements in quality of life and positive mental health made possible by the wider use of newer atypical medications should not be seen as offering a definitive long-term solution, but should be used as a spur to further research into the causes and more effective treatment of schizophrenia. 

Section 3

Review of selected literature

 

Pharmacotherapy for Schizophrenia

 

The first consideration of pharmacotherapy for schizophrenia came with the use of Rauwolfia alkaloids, first considered in 1931, and gaining considerable interest by the early 1950s (Baldessarini, 1985). Toxic substances, e.g., insulin, metrazol, were used to induce shock treatments. 

 

Prior to the inception of modern pharmacotherapy, e.g., tranquillisers, there was experimentation with hashish and cocaine.  LSD was synthesized in 1943.  Its psychedelic effects were later used for recreational purposes, as well as for investigating the human psyche.  Some psychotherapeutic benefit is proposed from LSD (Groff, 1994).  Research, although highly restricted, continues.  LSD came into disrepute when it was proposed as a chemical warfare agent, and when it was used by the US intelligence community in efforts to brain-wash subjects through a technique called "Psychic Driving”  (Andrews, 2001). Psychic driving was tested on unsuspecting hospitalized mentally ill people without their consent. 

 

A major breakthrough in pharmacotherapy for schizophrenia came with the introduction of chlorpromazine (1954).  In the search for new antihistamines, it was discovered that certain phenothiazines exerted not only a sedating effect but also a calming effect that seemed to reduce troublesome hallucination, delusion, and aberrant behaviour in the mentally ill. 

 

The following concise and informative history of pharmacological treatment for schizophrenia is presented by Lieberman, (1995), who states:

 

When antipsychotic drugs (APDs) were introduced in the United States in 1954 with the development of chlorpromazine (Thorazine), the treatment of schizophrenia was revolutionized. The initial reports of efficacy generated unbridled optimism in the mental health community and prompted many to entertain the belief that a cure for schizophrenia might be close at hand. However, in the ensuing four decades the enthusiasm of patients and clinicians alike was tempered as they painfully learned the limitations of antipsychotic drug therapy. Among these were that 1) not all patients have therapeutic responses, even to optimal APD treatment; 2) APDs are only effective against the psychotic (positive) symptoms, e.g., hallucinations or delusions, and are largely ineffective against the negative symptoms, e.g., emotional withdrawal, apathy and cognitive deficits (The negative symptoms are believed to underlie the disability in social and vocational functioning associated with schizophrenia.); and 3) APDs have an extensive side effect profile and cause clinically significant extrapyramidal symptoms (EPS) in almost two-thirds of patients.

 

Clearly, while extensive efforts were put into developing new drugs, it seemed that the side effect profile, and comparative efficacy, meant that newly developed medications from the three typical antipsychotic groups, phenothiazines, butyrophenones, and thioxanthenes, offered few advantages (if any) beyond the original chlorpromazine that was widely used from 1955 onward.

 

Atypical Antipsychotics

Efforts to find better medications eventually led to the advent of clozapine, in 1975, although deaths from agranulocytosis caused the drug’s withdrawal until 1990, when it was licensed with the proviso that a monitoring service assure that potential cases of agranulocytosis would be detected, and deaths prevented.

Since its inception and subsequent use, clozapine has demonstrated that there is a better way ahead in treatment for schizophrenia.  The vastly improved therapeutic benefits from Clozaril (clozapine) showed that new, more focused medications might reduce symptoms without blunting people’s consciousness and life experience; and without creating highly debilitating and sometimes permanently damaging side effects.  The drawback with clozapine was the continuous monitoring of blood counts, requiring blood tests at regular intervals.  This aspect certainly reduces acceptability of clozapine to service users.

In 1994 risperidone was introduced.  This second atypical offered many of the therapeutic results seen with clozapine, without the onerous blood testing and potential for life threatening blood disorder.

The pharmaceutical industry continued its quest for more selective, less toxic medications for schizophrenia.  In the last few years amisulpride, olanzapine, quetiapine, sertindole, and zotepine have been marketed.  While sertindole is currently withdrawn, these medications offer service users and psychiatrists a compelling choice of better alternatives. 

 

Studies Related to Atypical Antipsychotics

 

Numerous studies have been conducted evaluating comparative effectiveness of typical vs. atypical antipsychotic agents.  Following are studies related to olanzapine, a representative of the newest class of atypical antipsychotic agents.

 

Studies of Olanzapine

 

Numerous studies have examined olanzapine in comparison to typical antipsychotics.  These studies consider efficacy, quality of life, cost-benefit analyses, and numerous other outcome measures. 

 

For example, a randomised controlled clinical trial by Bhana N, Foster RH, Olney R, Plosker GL (2001) found:

 

The 1-year risk of relapse (re-hospitalisation) was significantly lower with olanzapine than with haloperidol treatment. In the first double-blind comparative study (28-week) of olanzapine and risperidone, olanzapine 10 to 20 mg/day proved to be significantly more effective than risperidone 4 to 12 mg/day in the treatment of negative and depressive symptoms but not on overall psychopathology symptoms. In contrast, preliminary results from an 8-week controlled study suggested risperidone 2 to 6 mg/day was superior to olanzapine 5 to 20 mg/day against positive and anxiety/depressive symptoms (p < 0.05), although consistent with the first study, both agents demonstrated similar efficacy on measures of overall psychopathology. Improvements in general cognitive function seen with olanzapine treatment in a 1-year controlled study of patients with early-phase schizophrenia, were significantly greater than changes seen with either risperidone or haloperidol. However, preliminary results from an 8‑week trial showed comparable cognitive enhancing effects of olanzapine and risperidone treatment in patients with schizophrenia or schizoaffective disorder.  Several studies indicate that olanzapine has benefits against symptoms of aggression and agitation, while other studies strongly support the effectiveness of olanzapine in the treatment of depressive symptomatology. Olanzapine is associated with significantly fewer extrapyramidal symptoms than haloperidol and risperidone. In addition, olanzapine is not associated with a risk of agranulocytosis as seen with clozapine or clinically significant hyperprolactinaemia as seen with risperidone or prolongation of the QT interval.

 

They comment on the cost-benefit equation, stating:

Pharmaco-economic analyses indicate that olanzapine does not significantly increase, and may even decrease, the overall direct treatment costs of schizophrenia, compared with haloperidol. Compared with risperidone, olanzapine has also been reported to decrease overall treatment costs, despite the several-fold higher daily acquisition cost of the drug. Olanzapine treatment improves quality of life in patients with schizophrenia and related psychoses to a greater extent than haloperidol, and to broadly the same extent as risperidone.

 

They conclude:

Olanzapine demonstrated superior antipsychotic efficacy compared with haloperidol in the treatment of acute phase schizophrenia, and in the treatment of some patients with first‑episode or treatment‑resistant schizophrenia. The reduced risk of adverse events and therapeutic superiority compared with haloperidol and risperidone in the treatment of negative and depressive symptoms support the choice of olanzapine as a first‑line option in the management of schizophrenia in the acute phase and for the maintenance of treatment response.  (Abs)

 

Numerous additional studies, e.g., Hamilton SH, Edgell ET, Revicki DA, and Breier A (2000); Purdon SE, Jones BD, Stip E, AU  - Labelle A, Addington D, David SR, Breier A, Tollefson GD (2000); Revicki DA, Genduso LA, Hamilton SH, Ganoczy D, Beasley CM (1999); Hamilton SH, Revicki DA, Genduso LA, Beasley CM (1998), provide ample evidence positive outcomes for Olanzapine. 

 

Quetiapine

 

A major study by Kasper and Muller-Spahn (2000) indicates:

 

Comparative clinical studies confirm that quetiapine is at least as effective as the standard antipsychotics, chlorpromazine and haloperidol and response rates with quetiapine are similar to those reported with other atypical antipychotics.  Quetiapine has also demonstrated superior efficacy to haloperidol in partially responsive patients, who can be particularly difficult to treat....

 

Uniquely among other first-line atypical antipsychotics, quetiapine is associated with a placebo-level incidence of EPS and an indistinguishable effect from placebo on plasma prolactin at all doses.... The consistent efficacy in treating all schizophrenic domains and good tolerability, particularly placebo-level EPS, make quetiapine acceptable to patients, as demonstrated in a survey of patient satisfaction. Thus quetiapine is a suitable first-line therapy for the treatment of schizophrenia and psychosis.

 

Numerous additional studies support Quetiapine as an effective and far less toxic medication compared to typical antipsychotic medicines.  A study by Möller (2000) indicates an apparently unique benefit of atypical medicines.  They conclude:

 

The results of controlled studies of the efficacy of the new atypical neuroleptics in treating negative symptoms show that these antipsychotics have a more pronounced effect on negative symptoms in acute schizophrenic patients than the classical neuroleptics. (Abs.)

 

The study points out the benefit of atypical agents in improving negative symptoms.  As MACA’s work is particularly focused on working with people with schizophrenia, we are acutely aware of the tragic, debilitating negative symptoms.  An exemplary study by Jibson and Tandon (2000) finds further evidence to support this view.  The study “Atypical Antipsychotics have Equivalent Efficacy in Treating Negative Symptoms of Psychosis” explains:

 

The range of baseline scores for the “Positive and Negative Symptoms Scale”  (PANSS), (Kay, Opler, and Fiszbein, 2001), negative sub-scale were similar across all studies....

 

Mean PANSS negative symptom sub-scale score improvements ranged from 1.5-6.8 for risperidone studies, 2.8-7.3 for olanzapine studies, and 2.9-7.4 for quetiapine studies. The magnitude of change from baseline with risperidone, olanzapine, and quetiapine was found to be similar....  <underline added>

 

They conclude: 

 

Data suggest[s] that quetiapine, risperidone and olanzapine are equally effective in treating the negative symptoms of schizophrenia. Atypical antipsychotics are generally more effective than conventional antipsychotics in treating the negative symptoms of schizophrenia and there appear to be no differences between them in this regard. Much, though not all, of this greater efficacy appears to be explained by their superior EPS profiles.  (Abs.)   <underline added>

 

This study confirms a finding from the Birmingham University study (cited below) that cautions that their endorsement of “Olanzapine as First and Second Choice” does not suggest superiority of one atypical preparation as compared to another.  The finding may have as much to do with the earlier approval for olanzapine.  From the perspective of the Birmingham University Study, the investigators seem to view olanzapine as a prototype atypical antipsychotic, much as chlorpromazine is accepted as a prototype for the old class of typical antipsychotics. 

 

When it was approved, olanzapine was the most advanced antipsychotic agent since risperidone was introduced.  Since that time, a number of medicines have come to market with similar efficacy / side effect profiles to olanzapine.  There is no conclusive evidence of superiority of one as opposed to another of these new medicines.  It should be noted, however, that differences are emerging. 

 

Atypical antipsychotic medicines have side effects, far less severe than the typical agents, however, sometimes they can be troublesome.  For example, excess salivation and lethargy can occur with clozapine.  This medication also requires regular blood testing, along with the risk of agranulocytosis that can result in death.

 

Other medications cause more or less weight gain.  It must be further cautioned that the long-term effects of these medicines cannot yet be assessed.  We all hope that effects as toxic as tardive dyskinesia will not emerge; only time and events will clarify whether atypical preparations are as safe as we hope. 

 

Clearly there are numerous very high quality studies that examine many measurable aspects comparing typical to atypical antipsychotic medications.  We cite one final study here that states a strong case for clinical guidelines for the treatment of schizophrenia. 

 

 

The Birmingham University Study

 

This study by Carole Cummins, Andrew Stevens, and Steven Kisely (1998), prepared by the Department of Public Health and Epidemiology at Birmingham University as part of a collaborative effort between the Wessex Institute and similar units elsewhere, provides a thorough and broad-ranging look at the pros and cons related to use of atypical antipsychotic medications, as opposed to the older, less expensive typical agents.  This study includes cost-benefit analysis, comparative cost analysis, and outcome measures related to pharmacotherapy of schizophrenia.

 

This study offers an extensive review of published literature pertaining to the arguments.  In the end, this study concludes that:

 

... Olanzapine is an effective and safe antipsychotic drug. In a short term trial with titrated doses of both drugs, olanzapine performed better than haloperidol with respect to mean changes in clinical rating scores and numbers of responders.... Olanzapine also has a better EPS side effects profile than haloperidol, and a superior effect on negative symptoms.... Olanzapine performs better than haloperidol in treatment of first episode schizophrenia and... olanzapine is associated with a better maintenance of response....

 

Olanzapine is superior to haloperidol in treating depressive symptoms. The evidence on these topics is based on sub-group analyses of the main trials and is somewhat weaker than evidence on overall efficacy. Although these results come from good quality studies, firm conclusions, in particular on the superiority of olanzapine to haloperidol in the maintenance of relapse, must await full publication of the results and possibly confirmation in further studies....

 

Olanzapine as first choice therapy had a cost advantage... over haloperidol....  The models presented here are relatively simple, but suggest that the use of olanzapine is likely to be at least cost neutral....

 

One area of uncertainty in the economic appraisal of olanzapine is its potential to cause tardive dyskinesia. No good quality evidence on this is available at present, and certain evidence will not be available until olanzapine has been in use for a number of years. As tardive dyskinesia is a serious and often irreversible side effect of existing neuroleptics that results in considerable distress and some physical disability in some 20% of conventionally treated patients, prevention of TD in treated schizophrenia patients would considerably increase the QALYs <Quality-adjusted life year measures> attached to the use of olanzapine in all settings, should olanzapine prove to have very low or zero risk of TD.

 

Summary

 

This review suggests that clinical and scientific evidence harmonises with our broader-based observations including assessments of clinical efficacy, side effect profiles, quality of life, and cost-benefit analyses, all pointing in the same direction - away from the old medications with their side effects (and side effect medications) and potentially devastating adverse health effects, toward an age in which pharmacotherapy for schizophrenia includes only the most efficacious preparations.  For once, moral-ethical imperatives and medico-economical views agree as to the correct course of action. 


Section 4

 

Methodology

 

This submission is intended to inform guidelines for the treatment of schizophrenia.  With this objective in mind, we chose to look at what MACA, as a national service-providing charity with over 120 years’ experience of supporting people with mental health needs, could contribute in the way of evidence.

 

We felt that our best contribution would derive from the wealth of direct information we could gain by looking at how our numerous mental health service users are actually prescribed for, and what differences, if any, we could document.  We wanted to examine what pharmacological approaches are in practice with service users, and how service users are responding to the psychiatric (pharmacological) treatment they are currently receiving.

 

One objective of our study was to ensure that our service users did not experience becoming passive subjects of a mental health survey.  We reject the pejorative labelling attached to being framed as a mentally ill person.

 

So, our approach did not infringe upon our service user’s lives.  Nevertheless, we were able to gain  meaningful statistical and qualitative data related to many mental health service users’ views on their current pharmacotherapy.  We also were able to gain a comprehensive, if cluster sample based, survey of prescribing practice in various regions and by health providers throughout the country.  We must caution that we do not hold this survey to be representative of prescribing practice generally. 

 

Keeping this in mind, the following describes the specific technical methodology used in the survey.

 

Technical Methodology

 

 

Selection of Subjects

MACA service users who are tenants in our residential care homes, and community based and supported homes.  MACA service users of whom we have experience or knowledge of their pharmacotherapy.

 

Operational Definitions for Constructs Used in this Study

 

 

Observed Change in Quality of Life

coded

OBSQOL

In this study, Quality of Life is measured rated on a 5 point scale by an observer.  The observer reports QOL change ranging from:

 

1  worse    2  no change    3  slightly improved    4  noticeably improved    5 dramatically improved

 

 

Observed Change in Mental Health coded

OBSMH

In this study, Change in Mental Health is measured rated on a 5 point scale by an observer.  The observer reports change in mental health ranging from:

 

1  worse    2  no change    3  slightly improved    4  noticeably improved    5 dramatically improved

 

 

Observed Side Effects coded

OBSIDE

In this study, Observed Side Effects are analysed on a before and after basis on a five point scale ranging from:

 

1  none          2  some            3  impairment             4  marked impairment             5  Crisis

 

 

 

 

Observer

In this study, the Observer is a near relative, if available and willing, or a member of the MACA service’s care staff who has known the service user for a long enough time to make informed observations. Often this will be the key worker.

 

 

Perceived Change in Quality of Life coded

USERQOL

In this study, Perceived Change in Quality of Life is measured rated on a 5 point scale by each service user.  The service user reports QOL change ranging from:

 

1  worse    2  no change    3  slightly improved    4  noticeably improved    5 dramatically improved

 

 

Perceived Change in Mental Health coded

USERMH

In this study, Perceived Change in Mental Health is measured rated on a 5 point scale by each service user.  The service user reports change in mental health ranging from:

 

1  worse    2  no change    3  slightly improved    4  noticeably improved    5 dramatically improved

 

 

Perceived Side Effects coded

USRSIDE

In this study, Perceived Change in Side Effects are service user rated on a before and after basis on a five point scale ranging from:

 

1  none          2  some            3  impairment             4  marked impairment             5  Crisis

 

 

Prescription Before

Each service user’s prescription prior to their last psychiatric review in which a change was made in a front line pharmaco-therapeutic agent.

 

 

Typical Medication Unit per Day

Prescriptions are evaluated on the basis of the clinical equivalents table specified in Goodman & Gilman (1995), or, if in conflict, according to the BNF41 guidelines.  Equivalence is computed by Typical Medication Units per Day are defined as the total daily dose of typical medications in units of equivalence to 500 mg chlorpromazine.   Depot injections of antipsychotic medications are given a bonus of one unit.

 

 

 

Ratios Applied to Compute

chlorpromazine

500

mg.

 

Standard Antipsychotic Dose

haloperidol

11

mg.

 

 

loxapine

80

mg.

 

 

sulpiride

600

mg.

 

 

thioridazine

350

mg.

 

 

trifleuperazine

10

mg.

 

RED TYPICAL...

droperidol

24

mg.

 

 

flupenthixol

12

mg.

 

 

fluphenazine

11

mg.

 

 

pericyazine

75

mg.

 

 

perphenazine

12

mg.

 

 

Pimozide

4

mg.

 

 

zuclopenthixol

25

mg.

 

 

clozapine

300

mg.

 

 

risperidone

5

mg.

 

BLUE ATYPICAL...

olanzapine

12

mg.

 

 

amisulpride

600

mg.

 

 

quetiapine

375

mg.

 

 

zotepine

150

mg.

 

 

Depot (any dose)

500 (1 unit)

 

 

 

Typical Medications

These medications are coded in RED above.

 

 

 

Atypical Antipsychotics

 

These medications include are coded in BLUE above.

 

 

Depot Injection

Deep intramuscular injection of antipsychotic agent prepared usually in a sesame seed oil medium for slow release over weeks.

 

 

 

 

 

 

Universal Psychotropic Dose

Typical  (TUPD)

Atypical (AUPD)

 

A unit of antipsychotic dose devised for this study.  This dose is theoretically equivalent to the average daily maintenance dose of chlorpromazine.  The UPD score is the ratio of dosing as applied to 500 mg chlorpromazine.  The equivalence was arrived at by using the median daily maintenance dose from Goodman & Gilman, The Pharmacological Basis of Therapeutics, Ninth Edition, 1995.  The British National Formulary  41 (2001) was referred to for medications not listed in Goodman & Gilman.

 

 

Side Effect Medication Score (SEMU)

Total units per day of side effect medications specifically one side effect unit =

5   mg procyclidine

50 mg orphenadrine

5   mg benzhexol

2   mg benztropine

 

 

Typical Dose Change Score coded

TYPCHANGE

A score derived from subtracting theTUPD before score from the after TUPD score.  The score illustrates the increase or decrease in use of TYPICAL antipsychotic medications

 

 

 

Atypical Dose Change Score coded

ATYPCHNGE

A score derived from subtracting the AUPD before score from the after AUPD score.  The score illustrates the increase or decrease in use of ATYPICAL antipsychotic medications

 

 

 

 

 

 

Side Effect Medication Change Score coded

SEMEDCHNGE

A score derived from subtracting the side effect medication units (SEMU) BEFORE and side effect medication units (SEMU) AFTER score.  This score reflects increase or decrease in use of side effect medications

 

 

Anxiolytic Units

coded

ANX_AFT

 

Daily units of anxiolytics on tablet = 1 unit basis

 

 

Antidepressant Score coded

ADEPRESCH

 

All antidepressants on a 1 tablet = 1 unit basis.

 

Polypharmacy score coded

POLY_AFT

The polypharmacy score counts one point for each prescription event of prescribing more than one agent in any single class of medications. Thus a person receiving both zuclopinthixol and chlorpromazine would get one point, if the same person got droperidol another point would be added.  By the same token, if diazepam is given with temazepam a point is scored.  If imipramine is given with fluoxetine, a point would be scored.  The construct represents a prescribing practice that is seen as increasing side effects while not increasing efficacy.  One would expect better life quality when polypharmacy is reduced.

 

 

Polypharmacy Change Score coded

POLYCHNGE

The score is derived by subtracting the polypharmacy before from the polypharmacy after score.  Negative numbers mean reduction in polypharmacy.  Positive numbers mean increased multiple prescribing.

 

 

  

Limitations in Methodology

 

This study uses a cluster sample that may be more or less representative of actual circumstances.  Application of findings should be tempered by the circumstantial differences between our subject population and any other population.

 

This study uses measures of association, rather than cause-effect findings. As with any non-blind study views may be affected by expectations. 

 

The research design does not utilise a control group.  As an ex post facto field based study a suitable control group would be difficult to identify.  The correlational statistics used assure a fairly high level of internal validity, however findings should be conservatively interpreted when applied to broader populations.

 

The in vivo design required very broad measures, i.e. global quality of life, global view of mental health, and simple evaluation of side effects.   The study does not aim to break down effects into more detailed or defined constructs.

 

Subjects mostly live in supported housing or residential accommodation.  Results should be interpreted with caution when applying our findings to more mainstream settings.  

 

This study excludes analysis of pharmacology unrelated to schizophrenia.  Statistics related to other psychoactive medications are reported but primary correlational hypotheses are not interpreted, except related to side effect medications that, we feel, relate specially to primary pharmacotherapy for schizophrenia.

 

Ethnicity, race, social class, and other minority group or sub-cultural or religious considerations are not considered here. We would welcome any future research focusing more especially on these issues.

 

The Questionnaire

 

A copy of the questionnaire is at Appendix A.  The questionnaire conceivesd a survey of the sample sent to the subject homes, and returned, by post, to the investigator.  The questionnaires were evaluated on the basis of the methodology described in this paper.  Data was analysed using Simstat <Korvac Computing> software that is verified as equivalent to SPSS in its capabilities.

Section 5

 

Findings

 

Introduction

 

Data was gathered from 189 service users from 31 MACA services. A breakdown of services by number of subjects and localities is shown under “Analyses of Variance” below.

 

As stated in Section three, this study used multiple correlations and analyses of variance to ascertain relationships in the data.  Findings are presented below.

 

Variables are abbreviated as follows

 

Row

OBSQOL          Observed Change in Quality of Life

OBSMH           Observed Change in Mental Health

USERQOL         Service User’s view Change in Quality of Life

USERMH          Service User’s view, Change in Mental Health

OBSIDE          Observed side effect change since medication review

USRSIDE         Service user’s view of side effects change since review

 

Column

TYPCHANGE       Change in prescribing typical agents after review

ATYPCHNGE       Change in prescribing atypical agents since review

DEPCHANG        Change in Depot injections from before to after review

POLYCHNGE       Change in polypharmacy after review

SEMEDCHNGE      Change in Side effect medication units after review

ADEPRESCH       Change in antidepressants prescribed after review

ANX_AFT         Anxiolytics prescribed after review

 

CORRELATION      MATRIX

               

 

                OBSQOL      OBSMH    USERQOL     USERMH     OBSIDE    USRSIDE

 

  TYPCHANGE    -.2804     -.2323     -.2282     -.2100      .2493      .1955

              (  170)    (  167)    (  163)    (  161)    (  166)    (  157)

              P= .000    P= .001    P= .002    P= .004    P= .001    P= .007

 

  ATYPCHNGE     .3718      .3756      .2410      .3464     -.3301     -.3427

              (  171)    (  168)    (  165)    (  163)    (  167)    (  159)

              P= .000    P= .000    P= .001    P= .000    P= .000    P= .000

 

  DEPCHANG     -.1991     -.2358     -.2124     -.1756      .2081      .2071

              (  169)    (  166)    (  163)    (  161)    (  165)    (  157)

               P= .005    P= .001    P= .003    P= .013    P= .004    P= .005

 

  POLYCHNGE    -.1400     -.1357     -.1100     -.0260      .1933      .1614

              (  169)    (  166)    (  164)    (  162)    (  165)    (  158)

              P= .035    P= .041    P= .080    P= .371    P= .006    P= .021

 

  SEMEDCHNGE   -.0266     -.0244     -.1661     -.0865      .0552      .0090

              (  169)    (  166)    (  164)    (  162)    (  165)    (  158)

              P= .366    P= .377    P= .017    P= .137    P= .240    P= .455

 

  ADEPRESCH     .1115      .1734      .1341      .1558     -.1102     -.0774

              (  169)    (  166)    (  164)    (  162)    (  165)    (  158)

              P= .075    P= .013    P= .043    P= .024    P= .079    P= .167

 

  ANX_AFT       .1230      .0790      .0999      .0845      .1345     -.0115

              (  175)    (  172)    (  171)    (  169)    (  171)    (  165)

              P= .052    P= .151    P= .097    P= .137    P= .040    P= .442

 

RED INDICATES STATISTICAL SIGNIFICANCE

CORRELATIONAL HYPOTHESES

 

Outcomes for the primary correlational hypotheses are reported in the correlation matrix.  Interpretation of these findings, as applied to the working hypotheses, are reported in the paragraphs to follow:

 

A. Is there an association between use of typical antipsychotic medications and measured outcomes?

 

               

                OBSQOL      OBSMH    USERQOL     USERMH     OBSIDE    USRSIDE

 

  TYPCHANGE    -.2804     -.2323     -.2282     -.2100      .2493      .1955

              (  170)    (  167)    (  163)    (  161)    (  166)    (  157)

              P= .000    P= .001    P= .002    P= .004    P= .001    P= .007

 

Correlations between use of TYPICAL antipsychotic agents with observer’s and service user’s quality of life, mental health and side effects

 

Interpretation:

 

There is a strong significant association indicating that as use of typical agents increase:

 

            there is a corresponding decrease in observed quality of life for service users.

 

            there is a corresponding decrease in observed service users’ mental health.

 

            there is a corresponding decrease in service users’ reported quality of life.

 

            there is a corresponding decrease in service users’ reported mental health.

 

            there is a corresponding increase in observed side effects.

 

            there is a corresponding increase in service users’ experience of side effects.

 

The evidence suggests that  increased use of TYPICAL antipsychotic medications are strongly associated with decreased quality of life and worse mental health, and greater side effects.

 

 

B. Is there an association between use of atypical antipsychotic medications and measured outcomes?

 

                                                                                               

                 OBSQOL      OBSMH    USERQOL     USERMH     OBSIDE    USRSIDE

 

ATYPCHNGE       .3718      .3756      .2410      .3464     -.3301     -.3427

                (  171)    (  168)    (  165)    (  163)    (  167)    (  159)

                P= .000    P= .000    P= .001    P= .000    P= .000    P= .000

 

Correlations between use of ATYPICAL antipsychotic agents with observer’s and service user’s quality of life, mental health and side effects

 

 

Interpretation:

 

There is a strong significant association indicating that as use of atypical agents increase:

 

            there is a corresponding improvement in observed quality of life for service users.

 

            there is a corresponding improvement in observed service users’ mental health.

 

            there is a corresponding improvement in service users’ reported quality of life.

 

            there is a corresponding improvement in service users’ reported mental health.

 

            there is a corresponding decrease in observed side effects.

 

            there is a corresponding decrease in service users’ side effects.

 

The strongest associations were identified between increasing use of atypical agents and improvement in mental health and quality of life, and significant reduction in side effects. Using these atypical agents holds much hope and promise for overall benefit to many service users.

 

 

C. Is there an association between use of depot injections and measured outcomes?

 

                                               

                OBSQOL      OBSMH      USERQOL    USERMH     OBSIDE     USRSIDE

 

DEPCHANG       -.1991     -.2358     -.2124     -.1756      .2081      .2071

                (  169)    (  166)    (  163)    (  161)    (  165)    (  157)

                P= .005    P= .001    P= .003    P= .013    P= .004    P= .005

 

Correlations between use of DEPOT INJECTIONS  with observer’s and service user’s quality of life, mental health and side effects

 

Interpretation:

 

There is a strong significant association indicating that as use of depot injections increase:

 

            there is a corresponding decrease in observed quality of life for service users.

 

            there is a corresponding decrease in observed service users’ mental health.

 

            there is a corresponding decrease in service users’ reported quality of life.

 

            there is a corresponding decrease in service users’ reported mental health.

 

            there is a corresponding increase in observed side effects.

 

            there is a corresponding increase in service users’ experience of side effects.

 

The evidence  suggests that increasing depot injections can lead to worse mental health and a decreased quality of life, while increasing side effects.

 

 

 

D. Is there an association between polypharmaceutical prescribing and measured outcomes?

                                               

 

                 

                OBSQOL      OBSMH     USERQOL     USERMH     OBSIDE    USRSIDE

 

POLYCHNGE       -.1400     -.1357     -.1100     -.0260      .1933      .1614

                (  169)    (  166)    (  164)    (  162)    (  165)    (  158)

                P= .035    P= .041    P= .080    P= .371    P= .006    P= .021

 

Correlations between polypharmacy and observer’s and service user’s quality of life, mental health and side effects

 

Interpretation

 

There is a significant association between polypharmaceutical prescribing and lower observed quality of life.

 

There is a significant association suggesting that as polypharmaceutical prescribing increases:

 

            there is a corresponding decrease in observed mental health

 

            there is a corresponding increase in observed side effects.

 

There is a significant association shown suggesting that service users experience more side effects when receiving polypharmaceutical prescriptions.

 

Service users’ responses to these questions about polypharmacy, quality of life, and mental health outcomes did not produce a significant  association. Nevertheless,  the evidence from the other questions suggests that polypharmacy is significantly associated with higher side effects, as well as a decrease in observed mental health and quality of life. 

 

E. Is there an association between use of side effect medications and measured outcomes?

                                               

                 

                OBSQOL      OBSMH     USERQOL    USERMH     OBSIDE    USRSIDE

 

SEMEDCHNGE      -.0266     -.0244     -.1661     -.0865      .0552      .0090

                (  169)    (  166)    (  164)    (  162)    (  165)    (  158)

                P= .366    P= .377    P= .017    P= .137    P= .240    P= .455

 

Correlations between changes in side effect medications and observer’s and service user’s quality of life, mental health and side effects

 

Interpretation:

 

While most responses did not give a significant association, there is a significant association - from users’ own responses - suggesting that as use of side effect medications increase there is a corresponding decrease in service users’ quality of life related to higher side effect medications.

 

 

 

Overall interpretation of Correlational Studies

 

These data provide a compelling case for the use of atypical antipsychotic medications in the interest of service users’ welfare. While individual patients must be given full information about treatments available and a view about what medication they wish to take, new atypical antipsychotics appear very significantly related to a better quality of life and better mental health for those with schizophrenia. 

 

These findings support the Birmingham University Study that advises atypical medications as first and second choice medications for schizophrenia.

 

Note: charts showing service users’ responses to Quality of Life questions on typicals and atypicals, and their views of the effect of atypicals on their mental health and side effects, are at Appendix B.

 

Return       CV   Peter Miles Berger.htm                     Main Page   personal.htm