35 replies to this topic

[TheBatman]

Another question for you... you don't think it's possible to reverse depressive symptoms without taking an antidepressant?

Lol wouldn't trust Tom just for the fact that he's a cocky. BTW depression is always just a temporary thing, and is also healthy when its short lasted, but some experience it more often than others. I'd say if a depression lasts longer than two weeks, you should look for help.

He can't say for sure that a stimulant or anything else won't work, cause everyone is different. Just because a med is labelled antidepressant doesn't mean it cures depression.

[Tom_]

Lithium Orotate lacks in any evidence of efficacy or safety and is pretty much the most dangerous non-prescribed drug people seem to take on this board. Lithium Carbonate or Citrate will reduce Noradrenaline as Badman said although I certainly wouldn't recommend it unless you come up against significant treatment resistance.

Depression is never healthy. Its a pathology that ends with death more often than it needs to. It certainly doesn't have to be a temporary condition, there are people who live with it for 30+ years never once in that time having achieved satisfactory remission. In general I agree with the two weeks mantra, although certain depressive episodes present unusually, such as recurrent brief depressive disorder. On the other hand studies indicate Depressive disorders tend to resolve in 6-8 months without treatment in the majority of people. This is unlikely to be the same for some sub-types. Melancholia may have a tendency not to resolve without treatment and a defining characteristic of atypical depression and chronic sub-clinical depression is treatment resistance and a chronic course.

People can fully recover from a depressive episode without medication, even without treatment as I said typically in 6-8 months. However risks of re-occurrence, treatment resistance and poor inter-episode recovery are much more common in not treated cases. Mild Depressive episodes often don't need anything more than doctors advice to 'look after oneself, follow good sleep hygiene, don't lock yourself away and a bit of exercise', unless there is documented good response or previous more serious episodes. Computer aided CBT will be of particular use in this population. If they become refractory to CBT/IPT medication and further therapy should be offered. In the case of moderate and severe depression Psychotherapy, Medication and lifestyle adjustments should be made as soon as possible. For rarer types of depression like chronic sub-clinical depression (dysthymia) medications are often a good place to start alongside Psychotherapy.

A stimulant might cover up the symptoms of Depression but there is almost no evidence that they will 'treat' the disorder. Stimulants might give someone the energy and motivation to make substantial lifestyle changes which will result in decreased depressive symptoms but the evidence clearly shows approved ADs, atypical antipsychotics and certain adjuncts are the only drugs which have a long term impact on depression.

[nowayout]

Tom, how clear is the evidence really regarding effctiveness of approved ADs for depression? There has been a lot of chatter lately on the weakness of the evidence and several respected academics have come out stating that ADs are at best only marginally more effective than placebo, if at all, based on metaanalyses including studies that were not piblished because they were negative, which practice created an artificial positive bias in the literature. What are your thougts on this?

[Tom_]

Unequivocally better than placebo. Somewhere between 20% & 40% percent more effective. In the case of less severe/chronic depressive episodes they are unlikely to be very effective. In fact NICE guidelines clearly indicate first line for presentation of mild depression be anything but pharmacological - something I emphatically agree with - except in the case of Chronic disorders or people with a history of more severe disorder.

STAR*D is the study to extrapolate from here. It clearly showed effect and didn't limit intake to the study based on only Depressive Episode as a diagnosis. A massive proportion of the depressed population have Psychiatric co-morbidity (ignoring non psychiatric co-morbidity) and pharmacological management of the depressive episode may well also be having an impact on other psychopathology. 1/10 inpatient admissions at least have a physical co-morbidity that may be effecting mental status. If these facts were controlled for, which they rarely are satisfactorily in studies an improvement in effect is likely.

The older studies show a much more significant effect of ADs (in general i.e. Mirtazapine, Meclobremide and the like may be exempt) and some have interpreted this as shoddy research. The reality is that studies from 30 years ago were using TCA's, MAOI's and the like. SSRI's are clearly less effective (and the most commonly studied now) and there use should be limited to first line agents (in less severe or non-sub-typed cases), for polypharmacy and when tolerance is a big issue. ADs are commonly prescribed not on the basis of symptoms but on general efficacy which is also a mistake.

I remain quite convinced that if rational pharmacy was studied in a large trial (atypical depression treated with Meclobremide, Melancholic with venlafaxine or Mirtazapine, 'typical' with SNRIs/Burpropion/Mirtazapine and then a rational evidence based progression including adjuncts, combinations etc) a much larger effect would be seen.

If you read a lot of the non-published studies they tend to have major methodological flaws (not always by any means).

Its also worth mentioning that the most effective and possibly worst tolerated of the treatment for depressive disorder remains non-selective irreversible Monoamine oxidase inhibitors. Adjuncts can be used to improve efficacy further and manage side effects when used safely and effectively. If a G.P can manage use of high potency opioids then there is no reason they can't follow a well set out algorithm for MDD including the use of MAOI's, which are seriously under used. Only when there is a significant risk of suicide, severe self-harm, complex co-morbidity, level four treatment resistance, psychosis or need for specialist psychotherapy and case management does a referral to Community mental health teams and Psychiatric input really need to be made.

I may have gone slightly off topic. In short my views are:

With the use of ADs as they currently are they are still more effective than Placebo and do reach significance.
A massive improvement in response is likely if a more rational algorithm is used, based on long standing evidence both controlled and from case studies.

[nowayout]

Okay.

The message I get (which you also touched on a bit, not to put words in your mouth (and which is actually relevant to the title of this thread, oversimplified as it may be)) is that depression does not really exist. Melancholic depression, atypical depression, etc., are very different diseases, and once trials start to distinguish and treat them accordingly with different drugs, we might start to see better results. (Though I would be the first counterexample to the particular drug matchup you mentioned as a melancholic unresponsive to mirtazapine.)

Edited by nowayout, 10 September 2013 - 03:46 PM.

[Tom_]

Depression does exist and all of them share some common etiology (SSRI's for example have SOME efficacy in all depressive disorder sub-types).

On the other hand there are also significant physiological differences. For example Melancholia has a tendency to present with raised cortisol, higher glutamate activity and lowered levels of GABA (Glutamate and GABA is much of a chicken/egg situation) while atypical depression is more likely to be associated with increased immunological and decreased metabolic activity. However both present with abnormalities of monoamine neurotransmition and both respond well to MAOI treatment.

The one study I've found actually suggests Mirtazapine is slightly more effective for Melancholia than Venlafaxine and in general Mirtazapine appears to be a better antidepressant, however its inappropriate for atypical depression due to increased weight gain.

http://www.ncbi.nlm....pubmed/11476127