Friday, March 5, 2010

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** For example,  in many of the early studies, lithium was abruptly withdrawn from controls, a practice now known to promote mania.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.

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