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Improving quality of life in schizophrenia

By Dermot - 18th Nov 2015

Quality of life as an important treatment goal in schizophrenia was the theme of a series of presentations at Irish hospitals recently.

The presentations were delivered by Prof Dieter Naber, Department of Psychiatry and Psychotherapy, University Medical Center, Hamburg-Eppendorf, Germany.

Prof Naber is the Lead Investigator in the QUALIFY (QUAlity of LIfe with AbiliFY Maintena) study, which showed the superiority of aripiprazole once-monthly compared to paliperidone IM injection when using the Heinrichs-Carpenter Quality of Life Scale (QLS). The QLS scale assesses the impact of deficit symptoms in schizophrenia on patient reported Health-Related Quality of <br /> Life (HRQoL).

QUALIFY is a 28-week, open-label, rater-blinded study, in which patients with schizophrenia who needed a change from their current oral antipsychotic treatment were switched to either aripiprazole once-monthly or paliperidone IM injection, another once-monthly atypical antipsychotic.

The primary endpoint results showed a statistically significant difference in improvement from baseline to week 28 on QLS total score, demonstrating non-inferiority to paliperidone IM injection by pre-specified criteria. Further investigations as part of the study established superiority of aripiprazole once-monthly to paliperidone IM injection. The respective changes from baseline to week 28 were 7.47 ±1.53 for aripiprazole once-monthly and 2.80 ±1.62 for paliperidone IM injection, with higher scores indicating better quality of life. Changes above 5.0 on the QLS scale can be described as clinically meaningful.

QUALIFY, which was backed by Otsuka and Lundbeck, is the first study to use the QLS scale to compare the effects of two long-acting injectable (LAI) antipsychotics with different modes of action in schizophrenia.

<h3><strong>Neglected issue</strong></h3>

Prof Naber told the <strong><em>Medical Independent </em></strong><em>(</em><strong><em>MI</em></strong><em>)</em> that quality of life in schizophrenia has been a somewhat neglected issue within psychiatry internationally. Feedback from Irish colleagues suggested that Ireland was no different. However, this situation has been changing.

“Very often, we the doctors are happy or satisfied if we can reduce symptoms, if we can improve the psychopathology,” noted <br /> Prof Naber.

Nevertheless, he said studies had shown that doctors and patients’ perspectives on success of treatment could sometimes “markedly disagree”.

Psychiatrists treating patients with schizophrenia tended to centre assessments around symptoms and especially positive symptoms. However, Prof Naber said it was vitally important to also seek information from patients about their social activities, social relationships and daily activities. This would help establish a “broader concept” of treatment goals.

<blockquote> <div>

Prof Naber said psychiatrists must go beyond reduction of symptoms and strongly elicit the patient perspective on both symptoms and quality of life. 

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According to Prof Naber, quality of life in schizophrenia was “totally neglected” for many years from a scientific research perspective.

 “I am sure that in the ‘60s or in the ‘70s doctors were already interested in the quality of life of their schizophrenia patients, but the first research papers were published in 1988, and then only a few per year,” he told <strong><em>MI</em></strong>.

“But in the last 10 or 20 years, the interest has markedly increased. Now, every year, there are several hundred publications on this topic. The reason, I think, is first of all we now have better ways to improve the quality of life because we have different drugs, and we also have different kinds of psychotherapy, so we can individualise treatment much better. Every patient is, of course, different.”


Different drugs have different side-effects and Prof Naber said it is the role of psychiatrists to investigate which drug best suits which patient.

“And, to do that, we should ask the patient which side-effects should be avoided by all means and which side-effects can be tolerated,” he said. “Sedation is a good example. For most patients, it is unwanted but for some patients it might be ‘wanted’, because they have trouble falling asleep. Weight gain for some patients is not good, but there are some patients who are under-weight and have trouble gaining weight, so for them it might be even an advantage.”

Prof Naber added that one of the key reasons why quality of life is neglected is a belief within psychiatry that patients with schizophrenia were not able to self-evaluate in a meaningful way.

“Or to put it in other words, that they are too ill to evaluate our treatment. Of course that is a bit paradoxical, because if we ask them about their symptoms and they tell us that they hear voices, we take that very seriously – it is the basis of our diagnosis.”

Nowadays, psychiatrists “listen more” to patients and receive their complaints and opinions much more seriously, he contended.


During his presentations, Prof Naber underlined the importance of adherence to medication in advancing quality of life goals – and the transparency that LAIs can have in this regard.

“If the patient does not come for the injection, then the doctor knows ‘we have a problem and I have to do something’.”

Another advantage of LAIs is the regular contact it promotes with the therapeutic team. Internationally there are some very successful clinics that align the intervals, when the patients present for the injection, with group, education and psychotherapy activities.

Additionally, mirror image studies have established that LAIs reduce risk of hospitalisation compared with oral antipsychotics (Kishimoto et al. <em>J Clin Psychiatry </em>2013;74(10):957–965), while a cohort study found LAI antipsychotics significantly improve treatment outcomes (risk of discontinuation or rehospitalisation) in patients with schizophrenia (Tiihonen et al. <em>Am J Psychiatry</em> 2011;168(6):603–609).

Prof Naber noted that, in RCTs, the benefits of LAI antipsychotics were not significantly superior to oral formulations. In contrast, as study design shifts toward prospective and retrospective studies in real-world clinical settings, LAI formulations display significant advantage, he outlined (Kirson et al. <em>J Clin Psychiatry</em> 2013: 74 (6): 568-575).

Nevertheless, Prof Naber stated LAI treatment is still underused for many reasons, one being the stigma associated with injectable medication in psychiatry. In one sense, it could be seen by patients as a ‘punishment’ for not adhering to oral medication. Additionally, it is also associated with the typical antipsychotic depots which carried strong side-effects.

Prof Naber’s view is that LAI treatment could be a vital component in improving and advancing quality of life. “To have vocational rehabilitation, to have social relationships, and all of this, you need a continuous treatment at least for a certain duration of life, and it is certainly much easier to get by good depot treatment. And it is still a problem that depot or LAI treatment is underused for many reasons.”

There is evidence that patients are willing to accept LAI antipsychotics when properly informed. However, there appears to be something of an information gap. In a survey of patients with/without LAI antipsychotic experience, some 79 per cent of patients without LAI experience cited having never been informed about the option by their psychiatrist. Some 75 per cent of psychiatrists felt that they informed the patient, but only 33 per cent of patients felt informed (Jaeger & Rossler. <em>Psychiatry Res</em> 2010; 175 (1-2): 58-62).

As regards the findings in QUALIFY, which found aripiprazole once-monthly superior to paliperidone IM injection on the QLS total score, Prof Naber noted that aripiprazole is not a dopamine agonist, but rather a partial dopamine agonist.

High blockade of dopamine receptors induces motor side effects, sexual dysfunction and also the inhibition of the reward system, he said.

Prof Naber said more options are needed when it comes to LAIs. Currently, there are only four atypical antipsychotics available as a depot.

“Our choice is rather limited compared to the oral medication where we have about eight or nine different atypicals available on the market, and so I hope that in the future that we will have some more drugs or antipsychotics available as a depot, to individualise treatment in a better way.”

In summary, Prof Naber said psychiatrists must go beyond reduction of symptoms and strongly elicit the patient perspective on both symptoms and quality of life.

Psychiatrists must also be cognisant of the “very important option” of depot treatment.

“Most doctors believe that ‘if I offer this depot treatment the patient will not accept it’. However, if we ask the patient they say ‘I have never been offered this kind of treatment’. So the reluctance is probably more in our heads and not so much in the heads of our patients.”

Relatives and caregivers tend to be supportive of the depot option. “They are very happy if they don’t need to ask their son every evening, ‘did you take your medication?’ Everybody hates this question – the patient and the relative hates it, and that is not necessary anymore with depot treatment.”


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