What Does ‘Relapse’ Mean? Definitions Used in Antipsychotic Trials Are Unclear

Joanna Moncrieff, MD
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We are told that long-term antipsychotic treatment reduces the risk of someone having a ‘relapse’ of schizophrenia or psychosis. What ‘relapse’ actually refers to in the studies that are supposed to establish this has not been examined, though. Our recent study of relapse definitions, published in Schizophrenia Research, shows that there is no consistent or agreed-upon definition of relapse in studies of long-term antipsychotic treatment, and that few of the definitions used can be confidently said to reflect a clinically significant psychotic episode.

Antipsychotic drugs are prescribed to people who are diagnosed with schizophrenia and other psychotic disorders on the basis of trials that demonstrate a higher rate of ‘relapse’ in people who are withdrawn from these drugs compared to those who continue to take them (Leucht et al, 20121). Yet, incredibly, there is no consensus about what ‘relapse’ means in this situation. If you ask clinicians they generally agree that a relapse indicates the recurrence of a clinically significant episode, characterised by psychotic symptoms and a substantial decline in functioning or increase in risky behaviours (Burns et al, 20002).

Yet I know from working in mental health services that the term ‘relapse’ can be used in a variety of different ways, and sometimes it is applied loosely to situations in which someone has shown slight changes in symptoms or functioning, without evidence that they are experiencing a full-blown episode of psychosis. This often happens because people — the individual themselves, for example, or their family members or professionals — are anxious about the possibility of relapse and therefore highly vigilant to slight changes in the individual’s behaviour or demeanour. Slight changes in mood or behaviour might, in some instances, be the precursor to a more significant deterioration, but this is not necessarily so, and they may instead just be the regular ups and down of that person’s experience.

So ‘relapse’ can mean different things to different people in the real world, but you would think there was a consistent definition of relapse in research studies, or at least a small number of definitions with similar criteria. But it turns out this is not the case. As part of the RADAR (Research into Antipsychotic Discontinuation and Reduction) study, the research team and I looked at the definitions of relapse that are used in trials of long-term antipsychotic treatment. We wanted to know how it had been defined elsewhere to help us decide how to define it in the RADAR trial (a randomised trial comparing a supported programme of antipsychotic reduction and discontinuation with maintenance antipsychotic treatment in people diagnosed with psychotic disorders). We found that dozens of different definitions have been coined. Over the last three decades, there are almost as many definitions of relapse as there have been studies!

Older trials conducted before 1990 often just used the ‘clinical judgement’ of the investigator or treating psychiatrist to identify relapse, the need to increase or re-start antipsychotic medication, or the need for other treatment or hospitalisation. Since the 1990s, trials have used increasingly complex combinations of alternative criteria, often including criteria based on changes in rating scales such as the Brief Psychiatric Rating Scale (BPRS) and the Positive And Negative Syndrome Scale (PANSS), alongside other criteria involving an increase in treatment or the presence of suicidal ideation, for example. There was no consistency in the way that rating scales were used to define relapse. Eighteen different PANSS-based criteria were used in the 23 trials that included a definition derived from the PANSS. The specified threshold for relapse varied between a 10 and a 30 point or 30% increase in the total score, for example, and in definitions that specified increases in individual item scores (such as those that concerned hallucinations or irritability) cut off scores varied from 3 (mild) to 6 (severe).

When we assessed whether definitions represented a clinically significant relapse — that is, one involving the presence of positive psychotic symptoms and a deterioration in global condition, functioning or behaviour of at least a ‘moderate’ degree or involving hospitalisation — we found that only seven trials fulfilled such criteria. It is possible that some more of the older trials were also looking at a clinically significant change, but it was impossible to tell because there were so few details, or relapse was just defined by the clinical judgement of the investigator or treating psychiatrist.

We found other evidence that recent trials, at least, are often focused on slight deteriorations in people’s mental state or behaviour rather than what would usually be considered a full-blown ‘relapse’. In trials where the definitions included changes in rating scale scores, the majority of those who were rated as having relapsed did so because they met the rating scale based criteria. These scales were measured during routine appointments, but if you think of the practicalities of this, how is it possible to do a rating scale with someone who is experiencing a significant episode of psychosis? People have to have capacity to take part in research assessments, and they have to have the attention span to fill in questionnaires. The fact that relapses were picked up during routine assessments much of the time suggests that they were not what would generally be considered a full-blown relapse. In fact, some of the studies acknowledge this, and the text refers to ‘impending relapse’ or early signs of relapse, but nevertheless they are presented as studies of ‘relapse prevention’.

What relapse consists of in these studies of long-term antipsychotic treatment is important for a number of reasons. First, if we don’t know what ‘relapse’ refers to in studies of long-term antipsychotic treatment, this might change how we weigh up that treatment. Long-term treatment is promoted because relapse is considered to be something that should be avoided at all costs. This is because a full-blown psychotic episode can cause considerable disruption to someone’s life and may lead to hospitalisation and other unwanted consequences. But milder fluctuations in symptoms may not be so problematic, and the benefits of preventing them might not outweigh the negative effects of using antipsychotics on a long-term basis.

Second, if relapse is defined as an increase in non-specific symptoms, these might be a reflection of antipsychotic withdrawal, rather than the recurrence of the underlying problem (Moncrieff, 20133). Antipsychotic withdrawal symptoms include anxiety and irritability, for example (Dilsaver 19884), which are included in rating scales like the PANSS, and are particularly likely to occur after the rapid discontinuation that occurs in most antipsychotic maintenance studies. Antipsychotic withdrawal may also precipitate psychotic symptoms (Moncrieff, 2006;5 Whitaker, 20106), in which case ‘relapse’ of a prior condition may be difficult to distinguish from a withdrawal-induced episode.

This study of relapse definitions doesn’t necessarily show that discontinuing long-term antipsychotics only leads to a mild increase in symptoms, but it does show that we need more evidence about what it does do exactly. We cannot take the meaning of ‘relapse’ in these studies for granted.

In the RADAR trial we decided to use rehospitalisation as the marker of a serious relapse, but we are also using a panel of experts (including people with lived experience) to identify episodes of relapse from blinded summaries of clinical notes. They will identify relapse on the basis of agreed criteria, which include a recurrence or significant increase in psychotic symptoms and a substantial change in behaviour or functioning that is sustained for at least seven days.

15 COMMENTS

  1. Your colleagues have started a special interest group: Evolutionary Psychiatry. Given the recent precedence of this turned out to be eugenics ending in mass destruction at six German psych ‘hospitals’ and then the concentration camps. I’m wondering what you think of this development. Relapse ?

  2. Dear Dr Joanna,

    This is an interesting point if it is approached scientifically, especially with the beneficial research work you do. I apologise for any cynicism.

    Otherwise, I think “Relapse” might depend on how the doctor might choose to describe the situation (even with standards in place).

    For example “Paranoia” could be described as Anxiety. Or “Psychosis” could be described as Hysteria.

    Severe Mental Illness categorization is supposed to refer to a person who is more disabled – than blind or in a wheelchair. So it’s difficult to say exactly what a Non Relapsing Severely Mentally Ill Person would be.

    I believe activist Will Hall recounted once in an article that he was incarcerated as acutely mentally Ill In a mental hospital until his insurance money ran out – and then discharged as well.

  3. In my twenties when I was coming off medication I ended up in hospital several times until I was able to finally reduce right down. And then I made full recovery and return to normal life – as the medications had been disabling me.

    I had complained about the “medication disability” but my Consultant Psychiatrist had kept this off my Records – even though he himself had stated “my disability” to be my Problem.

    For me Recovery depended on my Ability to deal with my Rebound High Anxiety.

    https://youtu.be/vdKs13kf13A

    “Mooji” wasnt around at this time but I found Psychologist “Dr Wayne Dwyer” very insightful.

    Eckharte Tolle ‘Power of Now’ also has good solutions which he says can be benefited from ‘organically’.

    (The psychiatric treatments break the mind and a person needs the right kind of help to recover).

  4. Psychiatry does need to mentally accept the reality that withdrawal from the psych drugs does cause a drug withdrawal induced “super sensitivity manic psychosis,” which is NOT a “relapse.” But I will say, such a drug withdrawal induced “manic psychosis” is infinitely less distressing, than is an antipsychotic and/or antidepressant induced anticholinergic toxidrome “psychosis.”

    The reason being is that an antipsychotic and/or antidepressant, anticholinergic toxidrome induced “psychosis” allows the “voices” of the satanic pedophiles to destroy your “mental health.” While a drug withdrawal induced “super sensitivity manic psychosis” allows the majority of the decent souls within the collective unconscious to help you heal. At least that was my experience.

    In other words, a drug induced “psychosis” allows the evil ones in to attempt to destroy one’s “mental health.” While a drug withdrawal induced “psychosis” allows the decent souls in, to help one restore their “mental health.”

  5. Hospitalization (or Crisis) can be caused by trying to come off “medication” too quickly.

    It took 6 years for me to taper from 25mg of Modecate Depot injection (maintenance dose) per month; to 25 mg per day of Thioradazine (tablet form) which is be about 8% of a (300mg Thioradazine per day) Maintenance Dose.

    I was okay with the 6 year time frame, as my disability came to an end, when I stopped taking the Depot Injection.

  6. Relapse means my wifes boyfriend is in town for the weekend and they would like the house to themselves. So ‘spike’ Boans drink with benzos, and when he collapses plant a knife on him for police to find and call mental health services to come and get him. A Community Nurse can then “loosely” apply the criteria required for incarcerating someone for the weekend (‘verbal’ a statutory declaration) and the now “mental patient” can be transported against their will to a cage where they can be taunted until they can be lawfully injected with enough tranquillizers to lay an elephant out for a week. (No National Standard as to what constitutes a “chemical restraint”. More loose definitions).

    Not such a good idea because I needed to clean up the mess from the party my wife had whilst I was locked in the cage.

    “Yet I know from working in mental health services that the term ‘relapse’ can be used in a variety of different ways, and sometimes it is applied loosely to situations in which someone has shown slight changes in symptoms or functioning, without evidence that they are experiencing a full-blown episode of psychosis”

    “Applied loosely”? From what I observed of Mental Health Services there were no standards applied (carte blanche) and zero accountablity for criminal action by public officers who are literally snatching citizens from their beds and force drugging them against their will for no other reason than someone wants it done. And imagine this Community Nurse lying to police and using them to torture and kidnap a citizen. No wonder he laughed when I said I would have something done about his criminality. Organised criminals are providing instructions to our police these days, and they are “just doing their job” lol

    The Community Nurse tells police “mental patient” and the whole mechanism of the State comes down on you with such a blow you’d be lucky to survive. Especially when the Operations Manager of the hospital investigates, uncovers the use of torture and kidnapping and then informs you they will “fuking destroy” you for complaining. They’ve got a reputation to protect, or at least in their delusional minds they have. Just don’t ask the patients, or as our Minister for Mental Health put it to Parliament regarding the large number of female patients being sexually assaulted, “you can’t listen to them, they’re mental patients”

    And why are they “mental patients”? Someone rang the hospital and said they didn’t agree with someone else so they have spiked them with benzos and planted a police referral on them so could you come and get them and change their minds please. One phone call and your status now changes from “citizen” to “mental patient” before they even leave the hospital. A little bit of torture disguised as medicine wouldn’t do any damage would it? Ask my daughter and grandchildren I haven’t seen for 8 years as a result if any damage was done.

    Still, I should be happy. Now that the Chief Psychiatrist and the Minister have confirmed in writing that arbitrary detention and the use of torture are lawful we should have no problems cleaning up the crime problems. They simply remove the protections afforded the public in the Act (no need for an amendment via Parliament either?) and neglect their duty to the public and hey presto were in a Police State. Forget the ‘soft’ tortures of Guantanamo, were going in ‘hard’ 🙂

    That was a bit silly writing to me as if the cover up had been effective. See being able to slander me as insane requires that the evidence to support what I am saying is not available. Now they have to neglect their duty because they can’t admit the truth, that they tortured and kidnapped me. What a disgraceful bunch of individuals they are, ………….. they smile to your face, …………and it’s your loved ones they claim to be caring for.

    • Had to rethink this because I forgot, Criminals have rights, Patients don’t. Hence why this Community Nurse (who is also a criminal) can commit his serious offences with little regard for the law. It actually protects him and dismisses the rights of those he commits his offences against. His trump card if you like. He is a criminal with rights (to not be tortured, kidnapped or unintentionally negatively outcomed), and his victims are slandered as patients without rights. Just as long as no one looks, and well given what I have been through believe me, no one looks. Police tell me they don’t even have copies of the Criminal Code in the Stations they are so badly resourced these days. And even when they do look (eg Chief Psychiatrist) they don’t like the truth, so conceal it with falsehoods. (Ie see the fraudulent documents sent to the Mental Health Law Centre). I assume they have rights when it comes to attempting to pervert the course of justice too?

      It does make an interesting study in human nature though when one actually sees what is done by those who see themselves as being above the law, and that the subjects of their ‘treatments’ are no longer seen as human. Philip Zimbardo was on to something.