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lisdexamfetamine (Vyvanse) for schizophrenia

S

seep

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Nov 28, 2008
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Lisdexamfetamine is being tested by its marketer on people with schizophrenia. Preliminary findings have already been collected. Source.

The subject pool actually includes only people with predominantly negative symptoms of schizophrenia (epidemiological studies say this is 20-30% of all schizophrenics).

I hate it when the government website doesn't include references for a trial. This is the first I hear of a serious effort to market amphetamine for schizophrenia. Needless to say,

  • I'd be very interested in a list of references on this, if anyone has access to one.
  • Any accounts by people diagnosed with schizophrenia who have taken amphetamine chronically to help them with their negative symptoms would also be interesting.

Thanks.
 
Not to be too Captain Obvious here, and maybe I haven`t kept up with the new research on schizophrenia (I haven`t), but doesn`t more dopamine generally equal worsened psychosis symptoms? Clearly, a consistent model for schizophrenia is more or less beyond our current understanding - it`s not as simple as reducing or increasing the amount of a few neurotransmitters in the head. But if antipsychotics (which generally lessen schizophrenic symptoms) typically antagonize dopamine receptors, how is this kind of therapy supposed to work?
 
Not knowing ANYTHING about this drug or its actions helping schizophrenia... I might guess that it helps in the same way that amphetamines help people with ADHD. The last thing I would think a hyperactive kid needs is an amphetamine.

Inedible said:
Not to be too Captain Obvious here, and maybe I haven`t kept up with the new research on schizophrenia (I haven`t), but doesn`t more dopamine generally equal worsened psychosis symptoms? Clearly, a consistent model for schizophrenia is more or less beyond our current understanding - it`s not as simple as reducing or increasing the amount of a few neurotransmitters in the head. But if antipsychotics (which generally lessen schizophrenic symptoms) typically antagonize dopamine receptors, how is this kind of therapy supposed to work?
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Yeah I thought it sounded crazy too at first, but it's about reducing negative symptoms in people whose positive symptoms are mostly supressed by antipsychotics. I imagine negative symptoms are worsened by antipsychotics, and that amphetamine induced elevation of dopamine levels in certain brain areas, while maintaining the dopamine blockade in whatever (other?) areas antipsychotics work on, could be beneficial.
 
Im amazed such a study was ever approved. I know one semi-functional girl diagnosed with schizophrenia who routinely abuses cocaine, amphetamine, methamphetamine, and methylphenidate, but she has to buy these from dealers. She is prescribed a high daily dose of quetiapine. She has never indicated that the stimulants help with her psychotic symptoms but that they help her 'get shit done'. So maybe they do not directly exacerbate psychosis in all people, but still, superficially dexamphetamine for schizophrenia sounds like prescribing LSD to treat HPPD.
 
hamhurricane said:
Im amazed such a study was ever approved
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It's interesting, yeah. Moreover for any trial to be approved a protocol has to be submitted to the FDA and this protocol has to give a solid rationale for the trial. This always involves a number of references to peer-reviewed articles (see the excellent protocols and investigator brochures that MAPS publishes, for instance). There are no articles for lisdexamfetamine as a possible treatment for schizophrenia on pubmed.

I'm just curious is all.
 
seep said:
It's interesting, yeah. Moreover for any trial to be approved a protocol has to be submitted to the FDA and this protocol has to give a solid rationale for the trial. This always involves a number of references to peer-reviewed articles (see the excellent protocols and investigator brochures that MAPS publishes, for instance). There are no articles for lisdexamfetamine as a possible treatment for schizophrenia on pubmed.

I'm just curious is all.
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I'm betting that there's some long forgotten research from the first half of the twentieth century (when the three basic psych drugs were barbiturates, amphetamines, and opiates) which showed promising results and wasn't continued because newer, "safer" drugs were developed. There's probably even some later research from the halcyon days of experimental psychology - amphetamines seem to have been tried as a treatment for just about every mental illness at some point.

This seems to have happened a lot over the last decade. It isn't that the original drugs didn't work, it's that they had unacceptable risk profiles. I can see how developing a new formulation which has a decreased risk profile might make a drug class which was once abandoned as a treatment option viable again. (Hell, in many cases doctors are choosing to prescribe the old style psych drugs these days over the newer "safer" ones because they're more effective in many people).
 
Amphetamines for schizophrenics, whatever next - dissociatives as a treatment for psychopaths! =D
 
Negative symptoms are things that are not present in schizophrenic persons but are normally found in healthy persons, that is, symptoms that reflect the loss or absence of normal traits or abilities. Common negative symptoms include flat or blunted affect and emotion, poverty of speech (alogia), inability to experience pleasure (anhedonia), lack of desire to form relationships (asociality), and lack of motivation (avolition). Research suggests that negative symptoms contribute more to poor quality of life, functional disability, and the burden on others than do positive symptoms.
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(from wikipedia)

Amphetamine is great for that stuff, but can cause the positive symptoms to get worse if that's not already treated with anti-psychotics (but in those trials only people already on anti-psychotics are included). There's nothing that quite works as good as amphetamine.. so I say its good news.
 
+1 to yoyoman for pointing out what the 'negative' symptoms of schizophrenia are. By contrast, 'positive' symptoms are those that are present in schizophrenics but not in healthy people, such as hallucinations, voices, delusions etc. It should also be stated that schizophrenia is a general term that encompasses several distinct subtypes of the disease with differing pathologies.

While amphetamine would likely exacerbate paranoid schizophrenia (the type most people think of when they hear the word schizophrenia. This type is primarily comprised of positive symptoms), I imagine it could help with catatonic schizophrenia (which is primarily comprised of negative symptoms).

It will be interesting to see if amphetamine causes positive symptoms in catatonic schizophrenics. This would be telling about the underlying neurochemical causes of the disease (i.e. do paranoid schizophrenia and catatonic schizophrenia have a common mechanism?).
 
It's not as simple as paranoid = positive and catatonic = negative. I've seen catatonics jogging in circles while saying the same three word phrase for 10 straight hours. Even a rigid stupor is a "positive symptom" if it's primarily a defense mechanism.

Schizophrenia (of any type) with predominantly negative symptoms is most often seen in patients whose conditions are in partial remission. It is known that amphetamine can precipitate a psychotic episode, which is why amphetamine is contraindicated in schizophrenic patients (just as Viagra is contraindicated in hypotensive patients).

But the pharmacokinetics of lisdexamfetamine are different than those of amphetamine. I'm actually really curious about this matter because I've been having trouble lately controlling my perception of reality while on Adderall. The experience shifts into something resembling psychosis rather quickly, every single day. Same goes for Adderall XR. I've never used Vyvanse, so maybe there's something there.
 
Probably isn't going to yield happy results for the pharmaceutical company, similar studies with ADHD drugs for persons with Bipolar disordered yielded generally bad results. Of course Shire Pharmaceuticals is responsible for this, no surprise there.

Let's look at Shire's amazing drug portfolio:
Adderall XR $1.1B Attention Deficit Hyperactivity Disorder (ADHD)
Vyvanse $318.9M Attention Deficit Hyperactivity Disorder (ADHD)
Elaprase $305.1M Hunter syndrome (lysosomal storage disorder) (Possibly the most expensive drug ever manufactured)
Pentasa $185.5M Gastrointestinal (Ulcerative colitis) (5-aminosalicylic acid, must've taken a lot of work in R&D to make this one)
Replagal $176.1M Fabry disease (lysosomal storage disorder) (An enzyme that they cloned)
 
I am sure those stimulants probably induced mania in those bp patients
 
I've read a book that claims OROS-methylphenidate and lithium worked quite well for ADHD/Bipolar comorbids... I don't have it here otherwise I'd look up the reference.
 
actually if I could have any Shire product I'd pick their recombinant human erythropoietin (Dynepo). Because of my lifestyle. Extreme endurance training is the ultimate euphoriant for me.
 
In the end, it comes down to weighing the pros and cons - are the beneficial effects on some symptoms worth the exacerbation of others?

In patients with predominantly negative symptoms (i.e. most parts of their brain have too little dopaminergic activity rather than too much), a major boost in energy and motivation may well be worth a minor increase in erratic behaviour.

I would even go as far as to say that if a (carefully-dosed!) stimulant can help a person sustain basic social relations, enjoy a hobby or hold a job, the stabilizing effect of a more stable environment may more than offset the drug's side-effects.
 
Hodor said:
In the end, it comes down to weighing the pros and cons - are the beneficial effects on some symptoms worth the exacerbation of others?

In patients with predominantly negative symptoms (i.e. most parts of their brain have too little dopaminergic activity rather than too much), a major boost in energy and motivation may well be worth a minor increase in erratic behaviour.

I would even go as far as to say that if a (carefully-dosed!) stimulant can help a person sustain basic social relations, enjoy a hobby or hold a job, the stabilizing effect of a more stable environment may more than offset the drug's side-effects.
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I'm presuming that it wouldn't be given as a mono-therapy anyway - that it would be given along with an anti-psychotic and mood stabiliser to minimise any over-correction.
 
maybe the people in the trial didnt have schizophrenia and were just infected with toxoplasmosis which appears like schizophrenia, making the trails wrong and leading to a generation of schizophrenia patients getting wronguflly treated D:

even tho that answer is doubtful never the less its just as possible as that trail result, maybe it did help even thought it shouldnt have, who knows, only time will tell.
 
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