Bipolar Research Issues

Bipolar disorder does not lend itself to adequately controlled double blinds with clear outcomes. This drawback applies to both pharmaceutical and orthomolecular studies.

Standard research is rarely conclusive because:
1 Changes in the cycling pattern can be confused with improvement. 
2 A measure which elicits a good acute response can, over time, increase deterioration.

3 Bipolar hypersensitivity to even mild stressors (e.g., the study) can alter results.

4 Manics may be uncooperative, or may readily drop out, distorting results. Hypomanias may not be obvious to the researcher, and unreported by patients.

5 Most studies are not long enough to account for cycling, rebounds, slowly-emerging improvement, long-term deterioration, etc.

Problems in accounting for biochemical individuality
1 Intricate interactions of treatment with individual biochemistry and health are difficult to control for.
2 Responsive subgroups may not be readily apparent.

Issues specific to pharmaceutical studies
1 Data on adverse effects is often lost due to the high drop-out rate common in pharmaceutical studies (Horrobin 2002).*
2 The effects of drugs, polypharmacy,  and drug discontinuation are not easily separated from effects of illness.**
3 The high cost of large double blinds largely shapes what is convincingly studied to proposals for which large pharmaceutical companies and other wealthy concerns are willing to pay.*** (Abramson 2004)
* Horrobin points out that typically, 40-60% of subjects drop out of six-to-eight-week studies of psychiatric medications (mostly to avoid side effects); in one-year studies, 60-90%. Benefits are thus validated for only a small percentage of patients.
** For example,  in many of the early studies, lithium was abruptly withdrawn from controls, a practice now known to promote mania. (Ketter 2001, Bauer 1996, Gold 1987)
*** Abramson (2004) claims that studies financed by drug companies are five times more likely to find in favor of the company's drug of choice.
 

Moral considerations 

The proposed treatment (or lack of it in controls) might trigger a new episode, promote rapid cycling, or otherwise increase illness severity, or fatality.  (Compton 2001)
To limit such consequences, current mainstream studies often compare a proposed medication to one already in use. This approach, unfortunately, makes conclusions about the new drug dependent on the lack of flaws in studies of the original drug.
This issue over depriving the control group also shapes nutritional studies. Doctors are loathe to deny bipolars what they believe are effective nutrients, for the sake of experimental results.


Evolving experimental design
Long-term naturalistic studies
Because of such factors, sufficiently controlled double-blinds studying bipolar treatment are unlikely. (Bauer 1996, Compton 2001) (So, for instance, despite prior "controlled" double-blind research, decades passed before recognizing that significant antidepressant use often fosters rapid-cycling, or otherwise worsens long-term outcome. (Post 2003, Ketter, Frye 2001))
Consequently, some mainstream researchers now recommend open, naturalistic, longitudinal studies, i.e., following patients over many years, probably decades. (Bauer 1996, Compton 2001 Ketter, Frye 2001)
This type of design particularly lends itself to exploring how bipolars fare over the long term, with multiple nutrients, tailored to health, diet, medication, evolving biochemistry, cycling pattern, etc.


Nutrient research

Nonetheless, although definitive conclusions may be years away, the research supporting orthomolecular approaches is promising. This research has entailed:

1 Double blinds and other controlled studies of certain key nutrients.

2 Outcome studies for multiple nutrients, usually tailored to individual biotype requirements. The best such study is probably Dr. Walsh's outcome data for 1800 bipolars, involving extensive biochemical and nutritive data on blood, urine, and hair, correlated with psychiatric rating scales and clinical results.
3 Other clinical data, especially that with lengthy follow-up.

4 Other nutritional/herbal research on associated psychiatric conditions (e.g., GABA’s effects on anxiety; valerian’s benefit to insomnia, etc.).
5 Research on nutritional, herbal, and medical therapies for confounding physical conditions (thyroid disorder, allergy, Candida, sugar imbalance, neurotoxicity, etc.)

For sources and further discussion, see my book, Natural Healing for Bipolar Disorder.

Some preliminary indications of nutritional outcome

Critical single nutrients
A number of small controlled or double blind studies restricted to specific critical nutrients (e.g., omega 3, various aminos, magnesium, vitamin C, etc.) have suggested considerable improvement, often comparable to pharmaceuticals short-term, and with a better profile long-term.*

Outcome with multiple nutrients
Not all isolated nutrients will be as effective Clinical results suggest multiple nutrients, accurately tailored to individual biochemical requirements, have the potential to compound the benefit significantly.

Thus, work with bipolars who fit certain "biotypes" is promising:
From accumulated data on over 1800 bipolars, given at least 90 lab assays each, Dr. William J. Walsh reports that of the approximately 80% of bipolars with biotype imbalances, 70% of those who stuck with the nutrient program (always an issue with bipolars) improved significantly; 50% eventually recovered to the extent that their physicians weaned them off medication. Results were best when biotype treatment was begun early. This may represent the best well-substantiated bipolar outcome thus far, whatever the treatment, either nutritionally or pharmaceutically-based. (Walsh 2007, 08)

Dr. Michael Lesser, MD, one of the early orthomolecular pioneers, similarly finds nutrient treatment  addressing biotype, other nutrient imbalances, blood sugar, allergies, immune status, liver function, etc, is successful in up to 85% of bipolars, "as long as the patient is dedicated to following treatment, and the family, supportive."  He states: "If they really cooperate, a tremendous amount can be done. Most can eventually go off medication. Others need minimal maintenance, but can work, go to school and do fine. Even if patients become frustrated, stop therapy, and go downhill, the overall outcome is still better than if they hadn't tried at all, because they have had the experience of the temporary gains." (Lesser 2008)


For more information, see Natural Healing for Bipolar Disorder

Warning: Intake of nutrients does not imply a change in medication, although with nutrient-based improvement, many physicians will cautiously reduce dosage.  The information in this blog is presented for education purposes only. If you need treatment for bipolar disorder, or any other medical condition, consult a knowledgeable physician. In some cases, this will be an orthomolecular or other nutritionally-oriented physician. 

*For instance:
Stoll AL, Severus WE, . Marangell LB, “Omega 3 Fatty Acids in Bipolar Disorder: A Preliminary Double-blind, Placebo-Controlled Trial,” Arch Gen Psychiatry, 56 (5): 407-12; May 1999. 
Kay DS, Naylor GJ, Smith AH, Greenwood C., “The therapeutic effect of ascorbic acid and EDTA in manic-depressive psychosis: double-blind comparisons with standard treatments,” Psychol Med, (14): 533-9; 1984.
Poldinger W, Calanchini B, Schwarz W, A functional-dimensional approach to depression: Serotonin deficiency and target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine, Psychopathology, 24(2):53-81; 1991.
Heiden, et al, “Treatment of severe mania with intravenous magnesium sulphate as a supplementary therapy,” Psychiatry Res, 89(3):239-46; 1999.

Nutritional therapies: Three Major Approaches

Nutritional therapies typically involve some combination of the following approaches, tailored to individual biochemical requirements:


1 Symptomatic: Nutrients are used to directly address mood.

     Stabilizing nutrients, usually lifelong, layered with mood-specific nutrients, when needed.

      For example, for bipolar depression: continue stabilizing nutrients; layer upon these, relevant antidepressant nutrients, using as mild a therapy as practical; taper off as symptoms remit.

Note: This approach is structurally similar to the mainstream pharmaceutical protocol (generally, mood stabilizers, lifelong, layered with mood and symptom-specific medication, when indicated). 
 


2 Nutrients to address relevant bipolar biotypes:

     Imbalances in neurotransmitter methylation.

     Pyrrole disorder.

     Metal metabolism issues.



3 Nutrient therapy for other underlying factors. These may involve:

    Specific nutrient requirements and/or imbalances.

    Health issues, e.g., allergies, blood sugar issues, hormonal balances,  Candida, malabsorption, seizures, toxicity, etc.

    Natural therapies to address diet, stress, and other lifestyle factors.

For more information, see Natural Healing for Bipolar Disorder

http:///www.boragebooks.com/bipolar.html


 
Warning: Intake of nutrients does not imply a change in medication, although with nutrient-based improvement, many physicians will cautiously reduce dosage.  The information in this blog is presented for education purposes only. If you need treatment for bipolar disorder, or any other medical condition, consult a knowledgeable physician. In some cases, this will be an orthomolecular or other nutritionally-oriented physician.