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Fiddian-Green, 2002 Depression: a metabolic perspective.


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Dr. Fiddian-Green presents an alternative theory of antidepressant "neurogenesis" in comments on a 2002 BMJ paper.

 

BMJ. 2002 Oct 26;325(7370):934.

Managing depression as a chronic disease: a randomised trial of ongoing treatment in primary care.

Rost K, Nutting P, Smith JL, Elliott CE, Dickinson M.

 

Source

 

Center for Studies in Family Medicine, Department of Family Medicine, University of Colorado Health Sciences Center, UCHSC at Fitzsimons, Aurora, CO 80045-0508, USA. Kathryn.Rost@UCHSC.edu

 

Abstract and full text at http://www.ncbi.nlm.nih.gov/pubmed/12399343

 

OBJECTIVES:

 

To evaluate the long term effect of ongoing intervention to improve treatment of depression in primary care.

 

DESIGN:

 

Randomised controlled trial.

 

SETTING:

 

Twelve primary care practices across the United States. Participants: 211 adults beginning a new treatment episode for major depression; 94% of patients assigned to ongoing intervention participated.

 

INTERVENTION:

 

Practices assigned to ongoing intervention encouraged participating patients to engage in active treatment, using practice nurses to provide care management over 24 months. Main outcome measures: Patients' report of remission and functioning.

 

RESULTS:

 

Ongoing intervention significantly improved both symptoms and functioning at 24 months, increasing remission by 33 percentage points (95% confidence interval 7% to 46%), improving emotional functioning by 24 points (11 to 38) and physical functioning by 17 points (6 to 28). By 24 months, 74% of patients in enhanced care reported remission, with emotional functioning exceeding 90% of population norms and physical functioning approaching 75% of population norms.

 

CONCLUSIONS:

 

Ongoing intervention increased remission rates and improved indicators of emotional and physical functioning. Studies are needed to compare the cost effectiveness of ongoing depression management with other chronic disease treatment routinely undertaken by primary care.

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28 October 2002 comment by Richard G Fiddian-Green http://www.bmj.com/rapid-response/2011/10/29/dual-effect-energy-deficit-hippocampal-neurogenesis

 

Dual Effect of energy deficit on hippocampal neurogenesis

28 October 2002

 

CNN reports today that whilst “stress” may suppress the regrowth of neurons (neurogenesis) in the hippocampus, putative site of learning and memory, antidepressants may stimulate neurogenesis (1). This fascinating report adds weight to the proposal that an energy deficit might be the cause of endogenous, or “major”, depression (2).

 

The initial response to the development of unreversed ATP hydrolysis and accompanying fall in tissue pH, precipitated by an impairment of mitochondrial oxidative phosphporylation, is protective (3). Growth factors are expressed and endothelial cell apoptosis is inhibited. The expression of growth factors is likely, therefore, to account for the neurogeneis reported by CNN to be induced by antidepressants. The problem is that as the severity of the energy deficit increases, and the severity of the accompanying tissue acidosis and rise in ionised calcium increase, the reverse occurs (4,5). Thus whilst the administration of antidepressants may indeed be beneficial in the short term they are likely to be harmful in the longer term especially if in impairing mitochondrial oxidative phosphoprylation they compound the severity of the energy deficit hypothetically responsible for the endogenous depression in the first place.

 

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28 October 2002 comment by Richard G Fiddian-Green http://www.bmj.com/rapid-response/2011/10/29/dual-effect-energy-deficit-hippocampal-neurogenesis

 

Might endogenous depression be the product of an intracerebral energy deficit? If so might it arise because the demand for energy, from glycolysis and ATP hydrolysis, exceeds the capacity to replenish intraglial glycogen stores and intraglial and intraneuronal ATP stores? An energy deficit, which may be present at rest but is more likely to be present upon provocation, might arise either because the demand for energy is excessive or because glycolysis and oxidative phosphorylation have been compromised by, for example, an antecedent cerebral injury or viral infection that uncouples oxidative phosphorylation.

 

The easiest and perhaps the first treatment that might be applied in addressing a cerebral energy deficit is the administration of coenzyme Q and other micronutrients that are needed for oxidative phosphorylation to proceed efficiently. In the case of depression complicating a head injury therapy might first be directed at reversing the effects of the cerebral injury. This might be effectively accomplished by reversing any impairment of oxygen and/or nutrient delivery by, for example, addressing any metabolically significant elevation in intracranial pressure, occlusive cerebrovascular disease and/or insulin deficiency present. Any uncoupling is best addressed by addressing the cause. If it is devitalised tissue or blood degradation products remaining after a head injury, consider removing them. ....Reducing the demand for energy is more challenging but conceivably possible with relaxation techniques, hypnosis, meditation and/or a good doctor’s reassurance and advice to take an old fashioned holiday.

 

Conventional drug therapy leaves much to be desired from the metabolic perspective and needs to be re-evaluated with some urgency. If administered to persons whose capacity for replenishing intraglial glycogen and intraglial and intraneuronal ATP stores is impaired mood elevators that act by enhancing neurotranmitter release and increasing the slope of neuron action potentials may compound the severity of the energy deficit present by increasing the demand for ATP hydrolysis beyond the capacity to replenish ATP stores Any severity of any energy deficit present is likely to be compounded by those antidepressants that impair mitochondrial oxidative phosphorylation. It might also be compounded by drugs used to treat co-existing cardiovascular disorders, notably beta blockers and statins. Of great concern is that any medication or mixing of medications that either induces or compounds the severity of an intracerebral energy deficit might increase the likelihood of developing neurodegenerative disorders in later years especially if the medications are administered for extended periods.

 

1. Fiddian-Green RG Delirium: a cerebral energy deficit?

 

bmj.com/cgi/eletters/325/7365/644#25750, 23 Sep 2002

 

2. Fiddian-Green RG Psychiatric aspects: an energy deficit? bmj.com/cgi/eletters/325/7362/454#25978, 3 Oct 2002

 

3. Fiddian-Green RG The real danger is in the mixing? bmj.com/cgi/eletters/325/7367/736/c#26113, 7 Oct 2002

 

4. Fiddian-Green RG Concerns about prescribing antidepressants bmj.com/cgi/eletters/325/7366/701#25874, 28 Sep 2002

 

5. Fiddian-Green RG Intracranial compartment syndrome bmj.com/cgi/eletters/325/7364/598/a#25555, 16 Sep 2002

 

6. Fiddian-Green RG Might statins cause Parkinsons? bmj.com, 18 Oct 2002

 

7. Misner BD. Coenzyme Q-10 Repletion bmj.com, 18 Oct 2002

 

8. Fiddian-Green RG . Coenzyme Q vs levodopa for Parkinson's. bmj.com, 21 Oct 2002

 

9. Madsen B. Re: Might statins cause Parkinsons? bmj.com, 23 Oct 2002

 

10. Fiddian-Green RG. Beta blockers and the risk of neurodegenerative disorders. bmj.com, 22 Oct 2002

This is not medical advice. Discuss any decisions about your medical care with a knowledgeable medical practitioner.

"It has become appallingly obvious that our technology has surpassed our humanity." -- Albert Einstein

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