Treatment of Acute Schizophrenia With Vitamin Therapy
Condition: Acute Schizophrenia
MeSH terms: Schizophrenia
Study type: Interventional
Phase: Phase 4

Summary: 
      Controlled studies using the orthomolecular approach have been few (Deutsch, Ananth, & Ban,
      1977). Those that were done were performed in chronic schizophrenia or in populations that
      included bipolar and schizoaffective patients. Both of these diagnostic groups are not today
      considered to benefit from the orthomolecular approach. Moreover, some negative studies of
      high-dose niacin were done in patients who were not otherwise given general counseling for
      good diet as described above. Therefore, this proposal is to study in a controlled manner
      carefully defined first onset schizophrenic patients using the protocol advocated by Osmond
      and Hoffer (1962). Patients can enter the study if they have been ill less than 1 year and
      are in their first hospitalization.
    

Detailed description: 
      Controlled studies using the orthomolecular approach have been few (Deutsch, Ananth, & Ban,
      1977). Those that were done were performed in chronic schizophrenia or in populations that
      included bipolar and schizoaffective patients. Both of these diagnostic groups are not today
      considered to benefit from the orthomolecular approach. Moreover, some negative studies of
      high-dose niacin were done in patients who were not otherwise given general counseling for
      good diet as described above. Therefore, this proposal is to study in a controlled manner
      carefully defined first onset schizophrenic patients using the protocol advocated by Osmond
      and Hoffer (1962). Patients can enter the study if they have been ill less than 1 year and
      are in their first hospitalization. Our Beersheba Mental Health Center is the only
      hospitalization facility for Southern Israel, population of half a million. There about 2
      thousand admissions to our hospital yearly and of those there are over 100 admissions with a
      diagnosis of schizophrenia or schizophreniform disorder for whom this is the first lifetime
      admission to hospital and their first episode of psychosis.

      Methods Study I - Open Pilot The pilot study will be carried out exactly as below, except
      without a control group. Results from the pilot will be evaluated before continuing to the
      controlled study, and protocol modifications presented to the Helsinki Committee if
      necessary. Ten patients will be studied in this open pilot study.

      Study II - Controlled Study, Not Blind Inclusion and exclusion criteria Patients can be
      accepted to the study age 18-30, if admitting diagnosis after review by the study coordinator
      is schizophrenia or schizophreniform disorder by DSM-IV. Since the diagnosis of schizophrenia
      may be difficult in the early stages of acute psychotic disease, cases in which the clinical
      diagnosis is consistent with and suspicious of schizophrenia (and inconsistent with bipolar
      disorder) even if they do not fulfill all the diagnostic criteria in DSM-IV will be accepted.
      Patients with alcohol or drug abuse in the last 6 months will be excluded. Patients with
      significant physical illness including peptic ulcer, or a history of hepatitis or baseline
      abnormal liver function tests will be excluded. Patients with mental retardation will be
      excluded. Baseline screening will be done for liver function (including AST, bilirubin,
      alkaline phosphatase and LDH) and blood glucose and then repeated after 6 weeks. Elevations
      of AST over three fold will lead to dropping patient from study. Patients who are unlikely to
      be able to continue in the study as outpatients will be excluded. Patients will be admitted
      to study only if this is their first lifetime psychiatric admission and their first episode
      of psychosis and only if history supports that they have been mentally ill for less than one
      year.

      Procedure Patients who enter the program will be treated with risperidone, 2-8mg daily at
      physician's discretion . They will be randomized according to a predetermined random order to
      vitamin regime or Centrum forte. Doses of risperidone will be lowered as clinically possible.
      Risperidone dose will be recorded weekly and will serve as a secondary outcome measure. A
      registered dietician will meet with each patient weekly and discourage refined sugar or
      excess fat and encourage regular fruit and vegetable consumption. High protein breakfast will
      be emphasized. Fifteen patients will be started yearly for three years.

      The vitamin regimen will be as follows twice daily with food:

        1. Ascorbic acid 1.5 g twice daily.

        2. 150 mg vitamin B6 twice daily

        3. Niacinamide 500 mg tablets, 3 tablets (1.5g) twice daily with food.

        4. Centrum Forte, one tablet each morning with food.

      The comparison group will receive Centrum Forte once per day.

      Outcome measures

      Patients will be rated with the Brief Psychiatric Rating Scale (BPRS) at baseline and weekly
      for 6 months. All patients will receive supportive psychotherapy both during the
      hospitalization and in clinic follow-up. Discharged patients will be followed in the
      outpatient clinic of the Beersheba Mental Health Center by a physician plus dietician team
      dedicated to this study. Each patient will be followed for six months. Outcome measures will
      be BPRS ratings over the course of the half year, readmissions, Global Clinical Assessment of
      function at the end of the half year, and risperidone dose.

      Skin test A blunted response of dermal erythema to niacin has been widely reported in
      schizophrenia, and it is possible that this response might predict clinical response to
      niacin treatment. All patients will have the Horrobin niacin patch test (Smesny et al., 2003)
      on admission to the study and it will be repeated after 6 months of continuous therapy.
      Niacin is applied simultaneously in four dilutions (0.1, 0.01, 0.001, 0.0001M) of 50microl
      each (approximately one drop of a standard eye-dropper) to the skin at the inner side of the
      forearm using chambered plaster for epicutaneous testing. After 90 seconds the plaster is
      removed. Skin reaction is quantitated at 3 minute intervals up to 21 minutes starting 90
      seconds after removal of the plaster.

      Risks The risks of high dose ascorbic acid have been reviewed extensively but these refer to
      doses such as 10g daily and the present dose of 3g daily is associated with minimal risk eg
      diarrhea. Doses greater than 3gm daily can cause increases in ALT and uric acid but risk of
      kidney stones has not been substantiated (Russel, 2005). Niacin at 3g daily is now widely
      used as a cholesterol lowering agent (Alpers, Stenson, & Bier, 2002) and is associated with
      minimal side effects or dangers eg, up to 5% increased glucose, elevations of liver enzymes
      and exacerbation in peptic ulcer, but these effects are rarely if ever seen with the
      derivative nicotinamide (Guyton, 2005). The other B-vitamins in the doses given would not be
      associated with any side effects.

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Intervention name(s): niacinamide; pyridoxine; ascorbate
Intervention type(s): Drug; Drug; Drug
Intervention MeSH terms: Pyridoxine; Niacinamide; Niacin; Nicotinic Acids
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: schizophrenia; niacinamide