Important distinctions in biochemistry need to be controlled forEffects of nutrients on other biological processes which might confound results.
And conversely, effects of individual biochemistry, epigenetics, and health on how nutrients are used.
Discerning relevant subgroups with distinct biochemical requirements and patterns of response.
Whether to use the entire complex of nutrients which work together toward a specific outcome or somehow control for the effects of using single nutrients isolated from that complex.
Sufficiently long studiesLong enough to assess nutrient benefit. Most nutrients and many herbs do not produce dramatic drug-like effects. But improvement tends to compound over the months and years.
And specificially for bipolar:
Most studies are too short to adequately account for the effects of cycling or shifts in cycling patterns.
Info on long-term effectiveness is critical* since treatments usually must be sustained for life (e.g., decades elapsed before it was realized that overuse of antidepressant drugs could trigger mania, increase cycling and worsen long-term outcome).
Moral considerations when studying bipolarHow morally can the researcher set up sufficiently lengthy controlled blinded studies involving nutrients (which are, by definition, critical to health), when he/she believes it likely that lack of those nutrient in controls could increase bipolar severity, possibly with permanent repercussions.
Additional issues specific to bipolar researchManic participation may be sporadic, or end abruptly, perhaps leaving only people with milder manias in the study.
People commonly do not report hypomania or mania; and researchers can readily mistake hypomania for signs of health.
Bipolar reactions to minor stressors, even the study, can distort results.
Biases favoring pharmaceuticalsHorrobin (2002) points out that 40-60% of subjects typically drop out of six-to-eight-week studies of psychiatric medications, mostly to avoid side effects. So info on drawbacks is lost, and the data is slanted toward positive outcomes.
Effects of drugs, polypharmacy, and drug withdrawal are not readily teased out from effects of illness. Medication rebounds, for instance, are often construed as bipolar deterioration (e.g., in many early studies, lithium was withdrawn abruptly in controls, a practice now known to promote mania).
The common protocol of comparing a new medication to one already in use presumes a lack of flaws in the original studies -- a notion often not borne out.
The high cost of large double-blinds skew the body of research away from substances like vitamins, which are unlikely to return enough profit to encourage much funding. Abramson (2004), moreover, finds research financed by drug companies is five times more likely (than if funded more impartially) to uphold the company's drug-of-choice.
The value of open naturalistic, longitudinal studiesSo while double blinds (with optimal controls) will always have their place, the complexity of factors involved, and the need long studies, have led a number of bipolar researchers (both mainstream and orthomolecular) to increasingly value open, naturalistic, longitudinal studies. Particularly when backed by periodic biochemical tests (and, as relevant, genetic tests), this type of design particularly lends itself to exploring how bipolars fare, long-term, with multiple nutrients, tailored to health, diet, medication, evolving biochemistry, cycling pattern, etc.
For an extensively-referenced compendium of nutrient-based approaches for bipolar disorder, see my book, Natural Healing for Bipolar Disorder.
You may also be interested in Natural Healing for Schizophrenia.
This information is presented for educational purposes only, and is not intended for diagnostic or treatment purposes. If you need treatment for mood disorder or any other medical condition, please consult a knowledgeable physician.