Managing depression as a chronic disease: a randomised trial of ongoing treatment in primary care
BMJ 2002; 325 doi: https://doi.org/10.1136/bmj.325.7370.934 (Published 26 October 2002) Cite this as: BMJ 2002;325:934
All rapid responses
There are several problems with your proposed method of treating
depression.
Although I am a retired psychiatric nurse, it doesn't mean I don't
still deal with many depressed people on a regular basis.
First, I don't believe a psychiatrist can make an accurate diagnosis
on a single visit. Patients don't start to reveal themselves until a
genuine trust rapport has been established. Information gathered on an
initial visit is likely to be extremely superficial and inadequate.
Remember, we're talking about people who are depressed. They are not
thinking clearly and usually forget to tell their doctors the most
important things the doctor needs to know.
Second, I have seen too many misdiagnoses and bad prescribing of
medications. The pharmaceutical monographs available on drugs are often
based on human trials with only healthy males on no other medication.
Thus, when a new drug comes out on the market, all the possible drug
interactions, adverse effects and contraindications have not surfaced yet.
Doctors are chronically poor at reporting adverse effects so they often
never get into print.
Unexpected paradoxical reactions can kill people or make them wish they
were dead. This has happened to a number of people I know who were being
treated for depression.
It can be difficult to find the correct drug and dosage the first
time. People taking any kind of, particularly psychoactive drugs, need to
be monitored closely and questioned carefully on a regular basis until the
effectiveness of the drug is determined and any adverse side effects have
been evaluated. Do you really want someone on the wrong drug suffering for
3-6 months getting worse instead of better?
Third, many people do not have active support networks to assist them
and family doctors have neither the time or training to help a person cope
with depression.
In closing, I am sorry to say that your comments suggest to me that
the best way to treat depressed patients is to give them a single chance
to express themselves, write a script and send them off to cope as best
they can. I find this an unenlightened approach to first-class patient
care.
Competing interests: No competing interests
There are at least two forms of "depression", imho: the "reactive"
and / or "neurotic" "minor", and the "major". Concerning the latter, I
agree that it will probably be a dysbalance of transmitters: that's the
way modern antidepressants work (serotonine and/or noradrenaline reuptake
inhibition).
With regard to the cost effectiveness of major and perhaps also of minor
depression treatment, I fear that it would make more sense to make the
patient go to a psychiatrist ONCE, let the psychiatrist make the diagnosis
and - if necessary - a drug prescription for 3, better 6 months, rather
than to occupy a GP or a nurse with visiting the patient several times for
3 or six months.
Competing interests: No competing interests
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. If it is chronic infection, such as
osteomyelitis, excise the offending bone and administer the appropriate
antibiotics. If uncoupling is due to a viral infection a monoclonal body
directed against the responsible cytokines, such as that directed against
TNF alpha, might be effective treatment. 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
Competing interests: No competing interests
Dual Effect of energy deficit on hippocampal neurogenesis
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.
1. Brain cell production may affect depression. CNN, Sunday, October
27, 2002 Posted: 6:58 PM EST (2358 GMT).
2. Fiddian-Green RG. Depression: a metabolic perspective. bmj.com, 26 Oct
2002
3. D'Arcangelo D, Facchiano F, Barlucchi LM, Melillo G, Illi B, Testolin
L, Gaetano C, Capogrossi MC. Acidosis inhibits endothelial cell apoptosis
and function and induces basic fibroblast growth factor and vascular
endothelial growth factor expression.
Circ Res. 2000 Feb 18;86(3):312-8.
4. Carbajo E, Lopez JM, Santos F, Ordonez FA, Nino P, Rodriguez J.
Histologic and dynamic changes induced by chronic metabolic acidosis in
the rat growth plate.
J Am Soc Nephrol. 2001 Jun;12(6):1228-34.
5. Reichert M, Steinbach JP, Supra P, Weller M. Modulation of growth and
radiochemosensitivity of human malignant glioma cells by acidosis. Cancer.
2002 Sep 1;95(5):1113-9.
Competing interests: No competing interests