CURRENT EVIDENCE FOR

THE MANAGEMENT OF
SCHIZOAFFECTIVE
DISORDER
 I

CURRENT EVIDENCE FOR THE MANAGEMENT OF

SCHIZOAFFECTIVE DISORDER
Introduction

Schizoaffective disorder (SAD) is an increasingly common diagnosis in psychiatry, however, it is still

controversial as a diagnostic concept and its management is largely unexplored ( 1). During its

formulation, there was significant debate on the possibility of removing it as a distinctive diagnosis

from the DSM-V (2). The atypical antipsychotic Paliperidone is the only medication approved by the

Food and Drug Administration (FDA) for the treatment of SAD, but clinicians often prescribe other

antipsychotics that have proven to be effective for SAD as well as mood stabilisers, antidepressants

and electroconvulsive therapy (ECT).

Schizoaffective disorder often occurs between the ages of 25 and 35 and is more prevalent in women

(3). The lifetime prevalence is approximately 0.3% and it is estimated that it comprises 10- 30% of all

hospital admissions for psychosis (3). The DSM-V characterises it as an "uninterrupted period of

illness during which there is a major mood episode concurrent with delusions or hallucinations,

where the psychotic symptoms last more than two weeks without a major mood episode" (4, 2).

There are two subtypes of schizoaffective disorder; the bipolar type (which involve manic and

depressive episodes) and the depressive type (which involve only depressive episodes) (4).

The symptoms experienced by individuals with schizoaffective disorder may vary but are

characterised by hallucinations or delusions and a manic or depressed mood. This may present as

disorganised thinking and speech, bizarre behaviour, impaired occupational and social functioning

and di fficulty with activities of daily living and self-care (5).

This essay will examine recent literature, published in 2009 and later, to outline the available

evidence for contemporary recommendations for the management of schizoaffective disorder with a

focus on the role of medications and electroconvulsive therapy.

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Case Presentation

JK is a 35-year-old, unemployed Malaysian female who was brought in by police due to a manic

episode in the context of medication non-compliance, sleep deprivation and a background of

schizoaffective disorder (diagnosed in 2015) and a traumatic childhood event.

History of presenting complaint

JK reports that she decided to stay the night at her partner's home and had forgotten her medication

at home. She did not sleep that night and the next day she was found screaming and throwing things

off the balcony. JK had called the Police as she believed she witnessed domestic violence occurring at

the house across the street. The Police then called an ambulance to escort her to the ED. JK also

reports she had felt unwell several days before admission, believing songs on the radio were telling

her she "need(s) to die before (she) can love again." JK also told ED staff that herself and her partner

had "the ability to raise their loved ones from the dead" and that "people are watching and following

(her) because they are jealous of (her) talent." JK denies any perceptual disturbances, thoughts of

self-harm, suicidal ideation of thoughts of harming others. However, she demonstrated pressured

speech, disordered thoughts, confusion, agitation, decreased need for sleep, sexual disinhibition,

limited insight as well as having grandiose and persecutory delusions and ideas of reference upon

admission.

Background information

JK is normally stable on lithium and desvenlafaxine (Pristiq), which was monitored in the community

by her GP. She lives alone in a town house, managing well independently, and uses Centrelink

benefits to support herself financially. JK has had previous diagnoses of depression in 2011 and

bipolar disorder, schizoaffective disorder and PTSD in 2015. She also had post-natal psychosis

following the birth of her daughter in 2008, whom is now twelve and is currently in the care of her

ex-husband. JK's childhood was marked by her father's suicide in 2001, when she was 16 years old,

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causing her to drop out of school in year 11. She admits that she still struggles with this and thinks it

is the reason for her low self-esteem and pessimistic personality type.

JK's first hospital admission was in 2011 due to d epressive symptoms. This was followed by multiple

hospital presentations in the following years due to suicidal ideation, self-harm and a suicide attempt

by hanging in 2015. Her mother, stepsister and cousin have untreated depression. JK has a good

relationship with her mother, who is her main source of support, and her daughter, who is an

important protective factor. She is currently in a supportive 4-month-old relationship with her

current partner who also has schizophrenia.

SAD Treatment: Literature Review

A systematic literature search was conducted using Western Sydney University, Cochrane and

PubMed databases for full text studies in English published in 2009 or later. The search terms used

included 'schizoaffective disorder treatment OR management' and 'schizoaffective disorder ECT.'

There were very few studies examining the efficacy of pharmacological and ECT treatment for a

specific patient sample diagnosed with SAD. Most guidelines and articles examine the efficacy of

treatment modalities on a sample of patients with schizophrenia and related disorders. In general,

patients with schizoaffective disorder have treatment regimens involving antipsychotics, mood

stabilisers, antidepressants and ECT.

Pharmacological treatment

Antipsychotics

As previously mentioned, Paliperidone (lnvega) was approved by the US FDA in 2009 for the

treatment of schizoaffective disorder based on three randomised control trials (RCTs)

examining its efficacy on an adequate sample size restricted to SAD patients (2). In a review

by Lindenmayer et al., the only studies investigating the efficacy of antipsychotics in a

specific SAD patient population include aripiprazole, risperidone, ziprasidone and

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paliperidone (2). The main finding of this review was that a higher dose of extended release

paliperidone (12mg/day) either as monotherapy or in addition to mood stabilisers or

antidepressant medication was safe and effective in the acute treatment of significant SAD

symptoms (2). One article included in this review also describes risperidone monotherapy to

be superior in symptom management for patients with the depressed type of SAD compared

to a combination of haloperidol and sertraline (2). Similarly, Jager et al. deduced that

risperidone appeared to have fewer side-effects than haloperidol without sacrificing efficacy

(6). Jager et al. identify only one analysable placebo-RCT that showed a ziprasidone dose of

160mg/day was more effective than placebo in improving scores in the Clinical Global

Impression-Severity (CGI-S) scale and the mean total using the Brief Psychiatric Rating Scale

(BPRS) (6). The general consensus of the literature is the recommendation to use atypical

antipsychotics such as paliperidone, ziprasidone, olanzapine, risperidone, quetiapine or

clozapine as first-line treatment of acute episodes of SAD (7, 8).

Combination therapy: adjunctive mood stabilisers and antidepressants

A study obtaining prescription data from SDI/Verispan's Prescription Drug and Diagnosis

Audit (PDDA) database found that 87% of patients with schizoaffective disorder received two

(48%), three (39%) or more pharmaceutical classes. That is, 93% of patients received an

antipsychotic, 48% received a mood stabiliser and 42% received an antidepressant. The most

common regimen prescribed is antipsychotic alone (22%), followed by antipsychotic plus

mood stabiliser (20%), antipsychotic plus antidepressant ( 19%) and antipsychotic plus mood

and antidepressant (18%) (9).

Lindenmayer et al.'s review raises the question of whether the use of multiple antipsychotics

is more effective than one, which was addressed in one study included in the review. This

study found that the combination of aripiprazole as an adjunct to quetiapine did not have

any advantage to a single anti psychotic on the management of psychotic and affective

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 symptoms of SAD (2). As previously mentioned, Lindenmayer et al. also describe risperidone

monotherapy to be more effective than haloperidol paired with sertraline (an

antidepressant). This may suggest, if patients treated with antipsychotic monotherapy

respond similarly to those treated with a combination of medications, that antidepressant

addition may not be necessary in the acute treatment of SAD.

Jager et al. also concluded, from the review of six RCTs investigating the efficacy of different

drug combinations, that lithium is superior to placebo as an add-on to clozapine, haloperidol

and to other antipsychotics (6). Lithium may also have a role in long-term SAD management

by having a preventative effect on affective relapse and cyclicity (9). Furthermore, another

RCT included in this review showed that haloperidol with placebo had an equivalent level of

efficacy as haloperidol paired with desipramine or amitriptyline (6), further supporting the

potential efficacy of antipsychotic monotherapy.

Regarding mood stabilisers, Jager et al. (6) identified a total of 6 articles in their systematic

review (two being RCTs), mainly exp loring their role in the long-term management of SAD. It

was demonstrated that fluphenazine and carbamazepine were superior to lithium in patients

with depressive and schizophrenia-like subtypes of SAD respectively in controlling mood

symptoms. However, multiple non-controlled studies in this review supported the clinical

efficacy of lithium, one study concluding that carbamazepine was equivalent to lithium in

efficacy. Unfortunately, the variation in the diagnostic criteria used in the selection of the

sample population in these studies may negatively affect the strength of this evidence.

Personal experience reports also suggest a role for antidepressants, but this remains to be

explored scientifically.

Electroconvulsive therapy (ECT)

In the Royal Australian and New Zealand College of Psychiatrists (RANZCP) clinical practice guidelines

for the treatment of schizophrenia and related disorders, several reviews and RCTs have shown that

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ECT, either alone or in conjunction with antipsychotic medication, increased rates of glo bal

improvement. One study included in the guideline found that the combination of ECT with

antipsychotics resulted in decreased rates of relapse of schizophrenia compared to either treatment

alone (10). Furth ermore, there was no evidence suggesting a difference in efficacy of bilateral or

unilateral electrode placement. An ECT guideline released in 2019 (11) recommends for ECT to be

considered a first-line treatment for severe psychotic symptoms as a good response is expected. This

recommendation for ECT as first-line treatment contradicts the guidelines of five of the most

authoritative psychiatric associations including The Royal College of Psychiatrists (RCP), World

Federation of Societies of Biological Psychiatry (WFSBP), American Psychiatric Association (APA),

RANZCP and Canadian Network for Mood and Anxiety Treatments (CANMAT) (9). In these guidelines,

ECT for schizophrenia is considered as a second-line treatment for medication-resistant patients.

On database search, there were no RCTs found within the last 10 years examining ECT efficacy in

patients with schizoaffective disorder. However, there were four retrospective chart analyses and

one case report found using a sample that was not exclusively SAD patients. Interestingly, one of

these retrospective studies based in Turkey found that the number of ECT sessions required for

patients with schizoaffective disorder was significantly greater than for those with bipolar disorder

and major depression. This study mainly sought to compare the outcomes of ECT using either

propofol or thiopental as the anaesthetic agent and found that patients that were given thiopental

experienced more respiratory and cardiovascular side-effects than propofol, which was associated

with fewer haemodynamic side-effects and shorter seizure duration ( 12).

Two articles identified that examined the efficacy of ECT include a retrospective chart review on

patients with schizophrenia or SAD (14) and a case report on a 67-year-old woman diagnosed with

schizoaffective disorder (13). The retrospective chart review included 20 patients over the age of 60;

65% of which with SAD and 35% with schizophrenia. The findings were that ECT was associated with

fu ll (60%} or partial remission (35%) of psychotic illness in 19 of 20 patients (95%). Minor adverse

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effects occurred in 20% (14). The case study observed that ECT, which was given for medication­

resistant SAD, gave significant improvement of mood and induced regression of delusional symptoms

(13). Although these two studies show good efficacy of ECT, weaknesses lie in the small and non­

specific sample populations.

The remaining two articles primarily examined the maintenance role of ECT in patients with

schizophrenia and schizoaffective disorder and concluded it is safe and effective in this population.

The first study included 20 patients (median age 64) diagnosed with schizophrenia and SAD during

long-term hospitalisation and found that ECT significantly reduced the Staff Observation Aggression

Scale for verbal aggression and self-harm score and improved the Global assessment of Functioning

score (15). The second study discovered that maintenance ECT (M-ECT) is effective for positive

psychiatric symptoms, including psychotic and mood symptoms, but not very effective for negative

psychiatric symptoms, such as apathy and catatonia. Under M-ECT, the mean duration of yearly

hospitalisation decreased by 80% from 10.5 to 2.1 months (SD 2.04) and patients saw improvements

in daily and occupational functioning (16). The number of SAD patients were in the minority for both

studies (4 of 20 and 8 of 19 respectively) and thus the strength of evidence for ECT efficacy in SAD is

reduced. Furthermore, bias may have been introduced in the second study as there was no

standardised method for symptom measurement.

Case outcome and Discussion

JK was treated with atypical antipsychotics (paliperidone injection and olanzapine), lithium, sodium

valproate and underwent 10 sessions of ECT over 6 weeks. Within two weeks, her manic symptoms

subsided but significant psychotic symptoms persisted. She developed some adverse effects of ECT

including temporary short-term memory loss and decline in cognition. Gradually her psychotic

symptoms subsided, and she had consistent improvements in memory and cognition during her 3

months stay. Shortly before discharge, she reported no psychotic or mood symptoms and was

discharged on a community treatment order (CTO) to ensure medication compliance.

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The treatment approach for JK involved two anti psychotics, two mood stabilising agents and ECT.

This multi-modal polypharmacy approach is in line with the tentative recommendations of recent

literature as she had significant and persistent psychotic symptoms and a good response to ECT

during previous hospitalisations. Given treatment compliance and continued contact with her GP and

psychologist, J K is likely to remain stable on her current medications. There may be potential to

modify or reduce the number of medications she is taking in the future given some evidence for the

efficacy of antipsychotic monotherapy (2). There may also be a role in the use of ECT as maintenance

therapy for J K, although this may not be indicated unless relapses become more frequent and

medication resistant (17).

The few number of articles obtained in this review of recent literature is the greatest limitation to

the evidence for the efficacy of antipsychotics, mood stabilisers, antidepressants and ECT in SAD

management. Many of these studies also utilised a sample that was not exclusive for SAD patients,

thus limiting the applicability to J K's case. The review articles mention a lack of relevant good quality

RCTs and the retrospective analyses report the possibility for bias due to inconsistent diagnostic

criteria and outcome measurement tools. Higher power studies with empirical data on an exclusively

SAD population and standardised methods of outcome measurement are greatly needed to support

the efficacy of this multi-modal approach in the treatment of SAD.

Conclusion

As demonstrated in JK's case, the evidence obtained suggests that combination medical therapy of

antipsychotics and mood stabilisers with adjunctive ECT (and a possible role for antidepressants) are

safe and effective in the acute and long-term management of SAD (2, 6, 7, 9, 12-16). JK reports no

more mood or psychotic symptoms and improved memory and cognition in response to ECT.

However, the evidence in this essay had low to moderate relevance and strength, thus more higher

quality studies are required to support this treatment approach.

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Future research

Despite increasing prevalence, research for the ideal management of schizoaffec tive disorder

continues to be largely neglec ted. There is a need for empirical research to be conduc ted on a

population with schizoaffective disorder only, rather than the grouping of individuals with

schizophrenia and related disorders. Studies should examine a wider range of treatment approaches

including pharmacological, ECT and psychotherapy to more thoroughly compare efficacy and

determine successful combinations of these treatment modalities. It is also valuable to further

explore differences in the efficacy of treatments for the SAD subtypes; bipolar and depressive.

Further research should also focus on o ther long-term management strategies for patients with SAD,

as maintenance ECT has shown good effect.

References

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17. NSW Health. Elec t roconv ul sive Therapy: ECT Minimum S tandard of Practic e in NSW

[Internet]. Wwwl.health.nsw.gov.au. 2011 [cited 25 M arch 2020]. Available from:

ht t p s ://wwwl.h eaIth.nsw.gov.au/pds/ActivePDSDocu ment s/PD2011_003.pdf

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