Medical Post Depression Interview - 2
By Dr. Shafiq Qaadri, MD
How many people in Canada are actually diagnosed with full depression?
One million Canadians can be expected to have a depressive syndrome at any given time. The lifetime incidence is approximately 8%.
That sounds like a fantastic number of people—does that not mean as doctors we’d be encountering depressed patients every fifth person or so?
That’s a reasonable approximation…Many family physicians note that about 20% of their population have a significant psychiatric component, and depression is the most common.
What is the difference between dysthymia, minor depression, the blues, and full depression?
Major depression is the most discrete and well-described. Dysthymic disorder used to be called depressive neurosis many years ago. It brings into play the requirement of suffering from depressive symptoms for a very long period of time—a minimum of two years. Some studies focus on individuals who have suffered for 8 or 9 years.
Minor depression is an additional diagnostic entity. We’re looking at the same timeframe as major depression, two weeks or more, but with a lesser number of symptoms, between 3 to 5. In many ways, somebody can be just as impaired, but they many not have the full number of symptoms…
As clinicians we realize that we don’t want to limit our therapies just because somebody does not have one extra symptom.
Are the terms endogenous and exogenous depression—meaning, from within and from without—being retired from psychiatry?
There was a landmark in this field in 1980.
Implicit in those terms was not only a notion of understandability of depression, either coming from within or reacting to an external event, but you also had developed a sense that certain symptoms belonged to one or other.
For example, the reactive depressed individual was said to have difficulty falling asleep and was more anxious, while the endogenously depressed individual was to have early morning awakening.
But then along came investigators like Eugene Paykel, who studied life events in relation to the onset of depressive episodes. He showed that, whether or not people had recent major life events, there was no distinction in the type of depression that they presented with.
Is depression gender-specific, or is making the diagnosis of depression gender-specific?
We do know consistently, right across the world, that women are affected in a ratio of 2:1 compared to men.
We also know that children before puberty are more likely to be 1:1. So clearly, reproductive biology is a factor…Now many people have looked not only at the biological issues, but they’ve also looked at the extra societal burdens on women. Another issue is that women consult family doctors and specialists more often than men do.
A related question is, do men actually present more often with addiction and alcohol-related problems?
Is declining testosterone—the whole issue of Andropause/menopause for men—another pathway to depression in men?
There have been a number of hormone supplementation studies, estrogen for women, testosterone for men.
The other issue is that the measurement of testosterone really requires the bioavailable testosterone, and many of the earlier studies were not doing this. There’s an assumption that low testosterone goes with low libido and other symptoms of depression…It is emerging anecdotally and in some clinical trials that testosterone plays an important role.
How should a family physician actually go about diagnosing depression?
There are issues of a quick screening. For example, we have a developed a 7-item version of the Hamilton rating scale, with questions on mood, physical correlates of anxiety, psychological anxiety or nervousness, work performance and suicide.
To make a more formal diagnosis requires a more elaborate history using, for example, the DSM IV [Diagnostic & Statistical Manual 4th Edition] criteria—depressed mood or a marked loss of functional activity, in addition to 4 or more of the other core symptoms.
What are the primary goals of treating depression?
I think we have raised the bar, in that people have the expectation of remission. On the rating scale, remission is virtually no symptoms; on the Hamilton scale, of the 17 items, it would be a score of 7 or less. On the 7 item scale, it would be 3 or less. So it’s an individual who by symptom standards, or indeed by observations of how they function at home or at work, they are, quote, “back to normal.”
Now that’s the expectation, but can we get there with every patient? The answer is that you can’t, but there is that expectation. In the past, I think we’ve too easily settled for, “Well, yes doctor, I’m a bit better”—but we need to explore more of the residual symptoms and functional activity…For example, sexual function may be a bit slower to come back to normal.
How prevalent is fatigue in depressed patients, and is there actually a biological cause?
I think that’s a good question. Our previous simplistic idea was, let’s treat the depression, and everything will go away: patients will sleep better, they’ll have more energy, they’ll be less anxious. In reality, people may be left with a number of residual symptoms, because our treatments may have targeted only one aspect, perhaps one brain circuit, in the depressive syndrome.
So fatigue, lack of motivation, and what we might call diminished executive function—like attention, organization, and planning capabilities—these symptoms are actually quite common.
There was a study, for example, that found over 70% of depressed patients complain of decreased energy.
What this has led to is the recognition that there are some antidepressants that are more energizing and activating, and others that are more sedating. We can also make a link between some of the neurotransmitters, like serotonin, noradrenaline, and dopamine, and these symptoms.
For example, the frontal cortex is where much of the executive and motivational processes occur, and we know that noradrenaline and dopamine are more important in these areas than serotonin. On the other hand, serotoninergic pathways are more important, for example, in the regulation of appetite and the sleep-wake cycle. So we know that we may have to make an intervention that deals with more than one neurotransmitter.
Are there serotonin receptor subtypes?
There’s over 20 different receptor subtypes. But the SSRIs don’t act, per se, on the receptors--they act to block the reuptake pump that’s taking serotonin back up again in the presynaptic neuron.
Can antidepressants protect brain tissue?
In animal models and laboratory studies, there’s a suggestion that antidepressants may stimulate brain-derived neurotrophic factor (BDNF). We know, for example, in animal models of depression or deprivation, the production of BDNF is shut down, and you may actually see a shrinkage of structures such as the hippocampi. An interesting thing with animals is that if you pretreat them with an antidepressant, you can preserve the BDNF production, and you can prevent the shrinkage of the hippocampi.
So this implies that the cascade of events from the neurotransmitter receptor can actually go down to the level of gene expression.
This implies that adverse circumstances in our lives, traumatic events and the like that lead to depression, may play a role in the shrinkage process of certain brain regions. So the antidepressants may act over the short term through the neurotransmitters, but over the long term through the release of substances such as BDNF.
Can you comment on the fact that part of the original selling points of the SSRIs was that they focused on one neurotransmitter—serotonin—yet the more recently released antidepressants are now targeting multiple neurotransmitters?
I’m very supportive of recent advances in antidepressant therapy. But we must acknowledge that in terms of overall effectiveness, ECT [electroconvulsive shock therapy], the old MAO Inhibitors such as Parnate, and the tricyclic antidepressants such as amitryptiline, are as effective as anything we have developed.
Of course, they have horrible side effects, the compliance rates are terrible, but the reason they are effective is the broad spectrum of action.
We then moved, as in other areas of medicine, to more selective and least side effect prone treatments. For example, Celexa [citalopram] would probably be in those categories.
What we are now moving to is medications with a slightly broader spectrum of action. For example, with Effexor [venlafaxine], we have both the norepinephrine and serotonin pathways acted on; or, with a drug like Buproprion [wellbutrin], both norepinephrine and dopamine pathways are acted on.
It’s always struck me as strange that things such as motivation, attention and energy—qualities that have a dopamine component—was not being tapped into in our antidepressant therapies, for example, with our serotonin drugs.
Putting extra weight on one side of the system can have multiple effects.
If a patient’s lead complaint is fatigue, are there any particular medications that you recommend, which might plug into more than one neurotransmitter system?
In a patient with fatigue, and perhaps oversleeping and listlessness, one would want to select more activating agents.
Buproprion, for example, has had that record for ten years in the US. It’s been a useful drug in that it hasn’t much of a side effect profile, and it does act in an activating way.
Some people might use a tricyclic like desipramine, and there are others…
Would you share with us some insights from studies in functional brain imaging?
PET Scans, or positron emission tomography, uses radio-labelled water or glucose, and using essentially a Geiger-counter type camera, we can look at areas in the brain that take up the glucose to a greater or lesser extent.
In general, the depressed brain does show a hypoactivity in the frontal areas and in some of the limbic regions, such as the amygdala; and other areas tend to be overactive. Our antidepressants seem to act in a way to neutralize these abnormalities.
We’re also looking at the difference between cognitive therapy and pharmacotherapy. There seem to be some brain areas that respond uniquely to drug therapy, and other areas that seem to respond uniquely to cognitive psychotherapy, and some areas that respond to both.
What’s your final message regarding the management and diagnosis of depression?
Don’t settle for a half-treated patient. Focus on residual symptoms, be aware that different antidepressants target different symptom clusters, use the drugs accordingly, and consider psychological treatments.
Dr. Shafiq Qaadri is a Toronto family physician and Continuing Medical Education (CME) lecturer. www.doctorQ.ca
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