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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by ed_uk on July 30, 2005, at 16:28:57
...........involving an old drug (which *isn't* a neuroleptic).......
Allopurinol, a widely used (and usually well-tolerated) anti-gout drug, may be a useful treatment for schizophrenia (and perhaps even schizoaffective disorder)...............
J Clin Psychiatry. 2005 Feb;66(2):213-9. Related
A clinical trial of adjuvant allopurinol therapy for moderately refractory schizophrenia.
Brunstein MG, Ghisolfi ES, Ramos FL, Lara DR.
Department of Biochemistry, Health Basic Science Institute, Federal University of Rio Grande do Sul, Porto Alegre, Brazil.
OBJECTIVE: To evaluate the xanthine oxidase inhibitor allopurinol as an adjuvant treatment for patients with moderately refractory schizophrenia, with the objective of increasing the endogenous pool of purines, including the neuro-modulator adenosine. METHOD: A double-blind, placebo-controlled, crossover clinical trial of add-on allopurinol (300 mg b.i.d.) for poorly responsive schizophrenia or schizoaffective disorder (DSM-IV criteria) was conducted. Thirty-five patients were enrolled, of whom 22 completed the 12 weeks of the study. Eighteen of these patients also completed a P50 evoked potential evaluation. RESULTS: Allopurinol was well tolerated and produced significant improvement in Positive and Negative Syndrome Scale (PANSS) total, positive, negative, and general scores, particularly for positive symptoms compared with baseline and with placebo phase. Nine patients improved more than 20% in PANSS total score during allopurinol treatment, whereas none responded in the placebo phase. Responders had a shorter duration of illness than nonresponders. P50 auditory sensory gating failed to improve with allopurinol treatment. CONCLUSIONS: Allopurinol was an effective and well-tolerated adjuvant treatment for poorly responsive schizophrenia, especially for refractory positive symptoms.
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Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):253-9. Epub 2004 Dec 28.
Beneficial antipsychotic effects of allopurinol as add-on therapy for schizophrenia: a double blind, randomized and placebo controlled trial.Akhondzadeh S, Safarcherati A, Amini H.
Psychiatric Research Center, Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, Tehran, Iran. [email protected]
There is a large amount of data showing that adenosine plays a role opposite to dopamine in the brain. Adenosine agonists and antagonists produce behavioral effects similar to dopamine antagonists and dopamine agonists, respectively. Allopurinol, a well-known hypouricemic drug that inhibits xantine oxidase, has been used as an add-on drug in the treatment of poorly responsive schizophrenic patients. Indeed, the neuropsychiatric effects of allopurinol in schizophrenia have been suggested to be secondary to its inhibitory effect of purine degradation, enhancing adenosinergic activity. The purpose of the present investigation was to assess the efficacy of allopurinol as an adjuvant agent in the treatment of chronic schizophrenia in an 8-week double blind and placebo controlled trial. Eligible participations in the study were 46 patients with schizophrenia. All patients were inpatients and were in the active phase of the illness, and met DSM-IV criteria for chronic schizophrenia. Patients were allocated in a random fashion, 23 to haloperidol 15 mg/day plus allopurinol 300 mg/day and 23 to haloperidol 15 mg/day plus placebo. Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and allopurinol showed a significant superiority over haloperidol alone in the treatment of positive symptoms, general psychopathology symptoms as well as PANSS total scores. The means of Extrapyramidal Symptoms Rating Scale for the placebo group were higher than in the allopurinol group over the trial, and the differences were significant in weeks 6 and 8. A significant difference was observed between the overall mean biperiden dosages in two groups. The results of this study suggest that allopurinol may be an effective adjuvant agent in the management of patients with chronic schizophrenia. Nevertheless, results of larger controlled trials are needed, before recommendations for a broad clinical application can be made.
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Int Clin Psychopharmacol. 2001 Jul;16(4):235-7.
Allopurinol augmentation for poorly responsive schizophrenia.
Lara DR, Brunstein MG, Ghisolfi ES, Lobato MI, Belmonte-de-Abreu P, Souza DO.
Department of Biochemistry, ICBS, UFRGS, Porto Alegre, Brazil. [email protected]
Adenosine has been proposed to contribute to the pathophysiology of schizophrenia and as a target for therapeutic intervention. In the lack of direct adenosine agonists, allopurinol may indirectly elevate adenosine levels by inhibiting degradation of purines. We report two cases of poorly responsive schizophrenic patients who improved considerably with add-on allopurinol 300 mg/day. Their clear clinical improvement warrant further investigation of allopurinol, as well as other purinergic strategies, for the treatment of schizophrenia.
~Ed
Posted by ed_uk on July 31, 2005, at 7:10:50
In reply to Schizophrenia: a new treatment option........, posted by ed_uk on July 30, 2005, at 16:28:57
Posted by ed_uk on July 31, 2005, at 7:40:44
In reply to Schizophrenia: a new treatment option........, posted by ed_uk on July 30, 2005, at 16:28:57
Posted by ed_uk on July 31, 2005, at 7:41:21
In reply to Schizophrenia: a new treatment option........, posted by ed_uk on July 30, 2005, at 16:28:57
Posted by ed_uk on July 31, 2005, at 16:37:25
In reply to Schizophrenia: a new treatment option........, posted by ed_uk on July 30, 2005, at 16:28:57
HA! Since it appears that no one is interested in schizophrenia, I was wondering whether allopurinol might be useful in the treatment of bipolar disorder.
In patients with schizophrenia, allopurinol was apparantly effective (as an 'add on' to APs) in controlling positive symptoms such as hallucinations, delusions and paranoia. Might allopurinol be an effective treatment for psychosis associated with bipolar disorder???? ....including psychotic depression, psychotic mania, and mixed episodes.
Allopurinol is an old anti-gout drug. It's very cheap and is extremely widely used. Although it's usually well-tolerated, serious hypersensitivity reactions occasionally occur....... a bit like Lamictal really!
Allopurinol inhibits an enzyme called xanthine oxidase. Xanthine oxidase inhibition prevents the formation of uric acid. As a result, allopurinol is used to prevent recurrent attacks of gout.
The Iranian study stated that.......
'There is a large amount of data showing that adenosine plays a role opposite to dopamine in the brain. Adenosine agonists and antagonists produce behavioral effects similar to dopamine antagonists and dopamine agonists, respectively. Allopurinol, a well-known hypouricemic drug that inhibits xanthine oxidase, has been used as an add-on drug in the treatment of poorly responsive schizophrenic patients. Indeed, the neuropsychiatric effects of allopurinol in schizophrenia have been suggested to be secondary to its inhibitory effect of purine degradation, enhancing adenosinergic activity.'
If allopurinol really does act as an indirect adenosine agonist, one might expect it to cause drowsiness........ caffeine, a mild stimulant, is thought to exert most of its effects via adenosine antagonism. Indeed, drowsiness has been reported as a side effect of allopurinol.
Caffeine can sometimes aggravate anxiety, especially panic disorder. I wonder whether allopurinol might be an effective treatment for panic disorder??? .........especially in those patients who react badly to caffeine. Patients who respond well to caffeine might dislike allopurinol. Just a theory.....
Caffeine, a convulsant, can aggravate epilepsy. Allopurinol appears to be useful in the treatment of epilepsy......... (further evidence that allopurinol affects the CNS)....
Epilepsia. 1991 Mar-Apr;32(2):279-83.
Clinical effects of allopurinol on intractable epilepsy.
Tada H, Morooka K, Arimoto K, Matsuo T.
First Department of Pediatrics, Toho University School of Medicine, Tokyo, Japan.
We studied the clinical efficacy of allopurinol as add-on therapy in 31 patients with intractable epilepsy. When administered for a short time, allopurinol was effective in 17 patients (55%); 8 were seizure-free, 8 had 75% decrease in seizure frequency, and 1 had greater than 50% decrease. Allopurinol was most effective in patients with localization-related epilepsy, especially in secondarily generalized tonic-clonic seizures. Allopurinol was not as effective in patients with Lennox syndrome or West syndrome, or in severe myoclonic epilepsy in infants. When allopurinol was administered greater than 1 year, its initial effectiveness continued in 8 of 14 patients who exhibited initial improvement. In 2 of the remaining 6 patients, the initial improvement disappeared during the course of treatment but control was regained by increasing the dosage of allopurinol. Mild side effects were observed in 4 patients (13%): drowsiness in 3 and abdominal pain in 1. Allopurinol may be a useful antiepileptic drug (AED), and a double-blind placebo-controlled trial should be performed.
~Ed
Posted by ed_uk on July 31, 2005, at 16:56:53
In reply to Schizophrenia: a new treatment option........, posted by ed_uk on July 30, 2005, at 16:28:57
Dipyridamole (Persantine) is a widely used anti-platelet drug. It is used to prevent thromboembolic complications following cardiac valve replacement. Dipyridamole is an adenosine reuptake inhibitor. Like allopurinol, it should theoretically act as an indirect adenosine antagonist.
J Clin Pharm Ther. 2000 Apr;25(2):131-7.
Dipyridamole in the treatment of schizophrenia: adenosine-dopamine receptor interactions.Akhondzadeh S, Shasavand E, Jamilian H, Shabestari O, Kamalipour A.
Roozbeh Psychiatric Hospital, Tehran University of Medical Sciences, South Kargar Avenue, Tehran 13334, Iran. [email protected]
OBJECTIVE: There is growing interest in investigating the adenosine-dopamine interaction in the ventral striatum. Adenosine plays a role opposite to dopamine in the striatum and adenosine antagonists, like caffeine, produce similar effects to increased dopaminergic neurotransmission in the striatum. In particular, a strong antagonistic interaction between adenosine A2A and dopamine D2 receptors takes place in the striopallidal GABAergic neurones. Therefore, adenosine agonists or uptake inhibitors provide a potential new treatment for schizophrenia. We undertook a pilot trial to investigate whether the combination of haloperidol with dipyridamole, an uptake inhibitor of adenosine, was more effective than haloperidol alone. METHODS: Thirty patients who met the DSM IV criteria for schizophrenia completed the study. Patients were allocated in a random fashion, 16 to haloperidol 20 mg/day plus dipyridamole 75 mg/day and 14 to haloperidol 20 mg/day plus placebo. RESULTS: Although both protocols significantly decreased the score of the positive, negative and general psychopathological symptoms over the trial period, the combination of haloperidol and dipyridamole was significantly better than haloperidol alone in decreasing positive and general psychopathology symptoms as well as PANSS total scores. CONCLUSION: Dipyridamole may be of therapeutic benefit in treating schizophrenia in combination with neuroleptics. However, a larger study to confirm our results is warranted.
Unfortunately, dipyridamole was not effective in anxiety..........
Biol Psychiatry. 1993 Apr 15-May 1;33(8-9):647-50. Related Articles, Links
Lack of efficacy of the adenosine reuptake inhibitor dipyridamole in the treatment of anxiety disorders.Stein MB, Black B, Brown TM, Uhde TW.
Section on Anxiety and Affective Disorders, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
We administered dipyridamole, an adenosine reuptake inhibitor, to 12 outpatients with DSM-III-R anxiety disorders (2 patients with generalized anxiety disorder, 10 patients with panic disorder). Dipyridamole was administered at a flexible dose in a single-blinded fashion following a placebo washout phase and elimination of placebo responders. The mean duration of active treatment with dipyridamole was 46 days (range 21-88 days); the mean peak dose of dipyridamole was 202 +/- 55 mg/day (range 100-300 mg/day). Symptom ratings were completed at regular intervals by the patient and by a research nurse unaware of the treatment condition. Clinically significant improvement in anxiety symptoms was not demonstrated. The implications of these findings for an adenosinergic dysfunction model of panic disorder are discussed.
~Ed
Posted by linkadge on July 31, 2005, at 20:33:46
In reply to Dipyridamole, schizophrenia, the role of adenosine, posted by ed_uk on July 31, 2005, at 16:56:53
If adenosine is low then why is there such a use of caffiene in schitsophrenia?
Linkadge
Posted by med_empowered on August 1, 2005, at 4:14:36
In reply to why the heavy caffiene use in schitsophrenia then?, posted by linkadge on July 31, 2005, at 20:33:46
high! Its long been known that those with schizophrenia have a tendency to consume MASSIVE amounts of caffeine (above 1,000mgs/day, or 10 or more cups, is pretty common) and they have a tendency to smoke...A LOT (I believe the average for someone with schizophrenia is a little over 2 packs daily, so 40 cigarettes or more a day). These tendencies are also found in those with bipolar disorder, but they aren't quite as common. Anyway, the best theory I've heard on this is that caffeine and nicotine are used to regulate the dopamine weirdness that accomapnies schizophrenia. Although the dopamine hypothesis of schizophrenia is pretty weak, this particular theory, I think, makes sense. Basically, since dopamine regulates so much related to drive and focus and well-being, caffeine and nicotine are consumed to kind of regulate dopamine weirdness...this may also be why those with schizophrenia have a tendency to abuse stimulants (cocaine, amphetamines) and pot rather than heroine, PCP, LSD, etc. Some people with schizophrenia may actually have less dopamine overall than a non-schizophrenic; that being the case, it makes sense to re-regulate the system by pumping it full of dopamine. It also (presumably) helps with the amotivation, flatness, apathy, and crushing depressive episodes seen in schizophrenia/schizoaffective disorders. When you factor in the heavy-handed use of neuroleptics, especially high-dose conventional antipsychotics, this behavior makes even more sense; caffeine and nicotine (and other stimulants) help to cushion the anti-dopamine effects of neuroleptics. Unfortunately, they also can screw with blood levels of the drugs--caffeine raises neuroleptic levels, nicotine lowers them-- but they offer some temporary relief. This kind of hints at a much more complicated, nuanced view of dopamine's role in schizophrenia than the oversimplified "schizophrenics make too much dopamine" view offered in the classic dopamine hypothesis. This more nuanced view is also behind some newer drugs for schizophrenia--particularly Abilify, which functions as a dual dopamine antagonist/agonist (and has similar effects on serotonin, as well). Apparently, the "next-generation" schizophrenia meds will probably be more Abilify-like than, say, Zyprexa-like in their dopamine actions. More meds will probably be used as well...Provigil, for instance, has been used in a couple of trials as an add-on for schizophrenia, with the hopes that it will help improve attention, motivation, and emotional expressiveness. It does help some people, but it can also make psychotic symptoms worse, so right now its a mixed bag.
Posted by xbunny on August 1, 2005, at 5:13:16
In reply to caffeine (and smoking) in schizophrenia, posted by med_empowered on August 1, 2005, at 4:14:36
I reckon one reason why schizophrenics consume more ciggies and coffee is because they are bored and restless (and perhaps that restlessness is in part due to the meds also). Maybe Im overanalysing the data but it seems to me that perhaps the studies of schizophrenics and smoking are mostly done in hospitals or day out patients kinda things. There NOTHING to do in hospitals except sit and smoke and I doubt many day out patients have jobs or much other occupying pursuits also.
Bunny (at 50grams of tobacco a week and over a litre of cola a day ;) )
Posted by xbunny on August 1, 2005, at 5:14:48
In reply to xbunny will be interested too..... (nm), posted by ed_uk on July 31, 2005, at 7:41:21
Yes it is interesting, thanks Ed.
Posted by ed_uk on August 1, 2005, at 13:50:28
In reply to caffeine (and smoking) in schizophrenia, posted by med_empowered on August 1, 2005, at 4:14:36
Hi Med! :-)
>This more nuanced view is also behind some newer drugs for schizophrenia--particularly Abilify, which functions as a dual dopamine antagonist/agonist (and has similar effects on serotonin, as well). Apparently, the "next-generation" schizophrenia meds will probably be more Abilify-like than, say, Zyprexa-like in their dopamine actions.
See........
http://www.pressi.com/dk/release/72252.html
Kind regards
~Ed
Posted by ed_uk on August 6, 2005, at 16:59:17
In reply to Dipyridamole, schizophrenia, the role of adenosine, posted by ed_uk on July 31, 2005, at 16:56:53
.....disorder ever take allopurinol or dipyridamole?????
~Ed
This is the end of the thread.
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