Hypothesis: Less is more Redux: Scheduled intermittent dosing to protect/prevent cognitive deterioration in schizophrenia

Abstract

We propose a strategy of scheduled intermittent dosing in place of daily administration of antipsychotic medications for the treatment of patients with schizophrenia.

Intermittent (extended) dosing has already been demonstrated to be at least equally effective as daily administration of antipsychotic medications.

It is increasingly appreciated that remission of positive symptoms is not the same as recovery: a resumption of a productive and socially gratifying life.

Our field has focused on positive symptoms to the exclusion of cognitive deterioration and emotional blunting. Dopamine is the primary neurotransmitter responsible for the accumulation and processing of new information as well as the expression of emotions modulated via the nucleus accumbens. Data suggests that patients receiving less accumulated antipsychotic agents do better over the years in achieving meaningful recoveries.

In addition to clinical improvement, there is the financial benefit in giving less medication, which is often costly, over several decades.

Finally, there is the possibility, albeit not yet demonstrated, that less accumulated antipsychotic agents might reduce the occurrence of significant weight gain, the metabolic syndrome, with its accompanying medical complications which not only impacts the quality of life and life expectancy of those who suffer from it, but also increases the financial burden to society.

http://www.medical-hypotheses.com/article/S0306-9877(16)00072-4/abstract

What do you think? Good idea or not?

In my simplicity I call it “medication holiday”. It is certainly not a bad idea from the perspective of liver and kidney health. Whether or not it is something a patient can responsibly self-manage is another kettle of fish.

I should clarify that I do it with my ADHD medication, which is primarily a dopamine reuptake inhibitor, so it is relevant to this study.

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For me that would mean a prolonged break from medication. Something more than intermittent.

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Yeaaap. It stems from when my mother organised my meds for me and I would take breaks from it during school holidays, so as to plump me back up and get my slept debt paid off a little.

However, 2 to 6 weeks duration is probably NOT a great idea for Sz.

Right now, I intermittently break from the stimulant based on my own personal observations - and when I don’t, my behaviours become increasingly obsessive and repetative, so the therapeutic nature of the drug is lost. Though I definitely get a LOT done - it’s just not necessarily stuff that needs doing haha

hey,

I’m sure it’s a worry. A lot of punters stop medications and try to get back on them to have no success or an incredibly increased dose to maintain function. Yeah…receptor occupancy is within the first 24 hours but success can be weeks to months away.

I think a reducing of dosage may work…stopping for any period seriously dangerous for ones mental health…but that is with our current technology. Next week we may have something better and all bets are off!

A friend in the struggle,

rogueone.

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I think it could easily become a scapegoat that directly interferes with patient insight and recovery. Definitely.

I’d like to add that each antipsychotic is different and it is very misleading and dangerous to categorise all anti-psychotics as possibly benefiting from intermittent cessation. This is further compounded by the complex individuality of each patient’s physiology. It is not a study that can be explored generally, as per the scientific method. Each drug will have to be studied in isolation, but even then the individuality of each patient will make the results potentially misleading.

It’s a dangerous proposition, but I can understand its potential if approached carefully and properly. It’s probably a study that should not be published in the public domain until it has reached sufficient maturity for all variables to be considered.

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They seem to be arguing from a “less is better” position. Certainly there’s a valid argument re giving the lowest therapeutic dose possible and that too high doses are counter productive.
However what may be a therapeutic daily dose may not be if taken intermittently.
Also people are a heterogeneous group as to how quickly antipsychotic discontinuation can have an adverse effect.
I know some here have said they go downhill rather quickly. Getting it right on a patient to patient basis would be tricky unless they are talking in terms of 2-3x a week dosing when the chances of relapse would probably be slight.

Right. I read about this ages ago, and tried it, and it ended up with me coming off meds. Just saying. It might not be a good idea if that happens.

Applying this approach to mental illnesses whose positive symptoms are characterised by loss of insight is playing with fire; plain and simple.

At least with ADHD, there is no inherent change to insight on or off of medication - assuming an absence of comorbidities anyway.

The full research paper is here:

http://linkinghub.elsevier.com.sci-hub.io/retrieve/pii/S0306-9877(16)00072-4

This is specifically what they are suggesting be researched - basically taking medications every other day (so skipping every second day):

We propose that APDs be administered to SZ patients utilizing
scheduled intermittent dosing after achieving remission of positive
symptoms via conventional daily dosing of APDs.

The schedule of
intermittent dosing would be determined on an individual basis
ranging from every other day to longer periods depending on the
response of each patient. Importantly, those patients who were
committed to treatment with APDs and had demonstrated compliance
would be appropriate for this regimen.

Our hypothesis of scheduled intermittent dosing offers a
rational approach to the treatment of SZ that may modulate the
problem of progressive loss of cognitive capacity either owing to
intrinsic properties of the diathesis [17] or conventional treatment
with APDs or both.

It would be interesting for researchers to test this theory out and see what happens, but I wouldn’t recommend people do this on their own as its just a theory right now with no evidence.

as they say near the end of the paper:

Rigorous testing of a scheduled intermittent dosing hypothesis
is relevant now, not only because of preservation of cognitive and
emotional capacity, but also because of potential benefits to physical
health.

It has not yet been demonstrated, but is not unlikely,
that reduction in APD dosing and particularly SGA might ameliorate
the metabolic syndrome observed in many patients: obesity,
hyperlipidemia, cardiac disease, hyperglycemia, and diabetes mellitus

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I don’t know about you guys, but if taking my meds wasn’t built into my daily routine, I’d forget way too often. I’d pretty quickly lose track of which is an on day and which is an off day.

I guess there’s an app for that :smiley:

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hey,

Yeah good point. Most antipsychs half lives are a day…except for some like Seroquel??? that is like 12 hours…so thus twice daily.

Anecdotedly I’d say it doesn’t have merit with our drugs but I guess no one has tried it. If people are willing to be test subjects then…we can only learn…but as meds may not work again??? could be a good cost to pay! Too much for sure!

Every second day? I do well and better than most but try to take pills same time everyday. It’s routine for sure and it works wonders. And I’ve played around with medications for years trying for better efficiency versus side affects so I used to try and take as low a dose as possible to maintain. These days I don’t change shite. I stay with what works and works well.

Can’t complain about that!

A friend in the struggle,

rogueone.

My pdoc has me taking half doses of Abilify on the weekends, although the half life of Abilify is so long I’m not sure it makes any difference.

This review assesses different intermittent drug techniques compared with maintenance treatment in people with schizophrenia or related disorders. Seventeen studies with 2252 participants compared intermittent drug techniques with standard maintenance on medication. Relapse was significantly higher in people receiving intermittent drug treatment. Hospitalisation was higher for people receiving intermittent drug treatment.

Results suggest that intermittent treatment is not as effective as continuous or maintained treatment in preventing relapse. Although information favours maintenance and continuous treatment, this is not always the case in real settings, where people may stop their medication due to debilitating side effects that affect their quality of life. More research is needed to assess any potential benefits or harm of intermittent treatment, particularly regarding the side effects commonly associated with maintained antipsychotic treatment. There was no exploration of economic/money savings, specifically relating to the potential cost-effectiveness of intermittent techniques.

Until further evidence is available concerning the potential benefits or harms of intermittent treatment, managers, psychiatrists and policy makers should consider it an experimental therapy.

Yeah. It’s fire. Playing with it.