Curbside Questions: Brief answers to clinical queries

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Curbside Questions: Brief answers to clinical queries


Question: I wanted to ask about the first confrontation of the patient with a depressive condition (not related to the subtype of depression), but rather the criteria that you consider fundamental to say that a person is in clinical depression.

PL: PL likes the term "clinical" depression (rather than "major" which was invented by DSM-III to contrast with "minor," later dropping the latter. The term "clinical" implies that the depressive symptoms are severe enough to reach clinical attention, meaning visiting some kind of health professional. This clinical attention could involve intervention with drugs, psychotherapy, or neither (watchful waiting). DSM terminology tends to emphasize the concept of functional impairment, but sometimes people can function normally at work or at home, and still have severe depression, even receiving clinical attention. So for PL, the concept of clinical depression is, in part, a proxy for severity: a depression severe enough to be beyond the bounds of typical sadness in human experience. PL would not emphasize the number of symptoms, nor the 2 week minimum of DSM. Rather, such symptoms do tend to last months when severe, and usually involve more than just one or two symptoms.


Question: Can we hear your a comment on this new Cochrane review of valproate in acute mania?

PL: This meta-analysis concludes that valproate is effective in acute mania, which is obvious based on multiple studies. There are few studies in adolescents, so efficacy there is not proven. It is claimed that valproate is less effective than dopamine blockers, like olanzapine and risperidone, which may be true, but the olanzapine studies are misleading. One was conducted by Eli Lilly, the maker of olanzapine, and it dosed valproate low; it found more efficacy with olanzapine. Another was conducted by Abbott Laboratories, and it dosed valproate high; it found more efficacy with valproate. These important clinical nuances get lost in meta-analyses. The mean level of valproate that was effective in its FDA-labeled trials for acute mania was in the mid 90s. At such high levels it is effective, and it may be similar to neuroleptics. However, some patients may have trouble reaching those doses. Thus, the PL view is that high dose valproate is effective in acute mania by itself, but in most people, dopamine blockers remain easier to dose and are very effective for acute mania. There is an old literature, also, that neuroleptics were more effective than lithium in acute mania. PL does not doubt that dopamine blockers are rapid beneficial treatments for acute mania. But they are not "mood stabilizers," for the reasons provided on the PL March 2016 newsletter, and do not have the longer term benefits seen with lithium and valproate.


Comment: One impression from the local scene is that over-reliance on “atypical” monotherapy for maintenance is increasing. (Antidepressants continue to be mistakenly prescribed, as well.) Prescribers are unaware of the problems with the enriched design. Of even greater concern: they have an irrational fear of lithium and appear to know little about its ability to prevent suicide and relapse into depression.

PL: Thanks for this excellent comment. The link above explains why PL does not think that dopamine blockers are "mood stabilizers" and thus should not be used in long-term treatment of bipolar illness by themselves. The problem of the "enriched" design is key: patients are preselected to be treatment responders to the dopamine blockers before the maintenance study begins. This biases the study from the beginning and produces invalid results, as explained in the PL newsletter here.

On the irrational fear of lithium, what can PL say? It is irrational itself.


Question: A patient of mine who is on oxcarbazine is concerned about the article that just came on in JAMA about anticholinergic medications and dementia.  I am not aware that oxcarbazine has prominent anticholinergic properties. Can you comment on this please?

PL: Anticholinergic agents have direct impairment on cognition; whether this leads to dementia long-term is much more questionable, and doubtful in the PL view. Oxcarbazepine has no anticholinergic effects; unfortunately it's also basically ineffective for any psychiatric uses.

Question: You recommend the TEMPS scale to assess mood temperaments. Do you know where the questionnaire can be obtained? I can not find it online.

PL: The TEMPS scale has been published in multiple different papers in different lengths. PL prefers the 50 item scale which is reasonably brief and patients can fill it out in the waiting room. The original 50-item paper can be found here, with the scale in the appendix. However, the paper doesn't provide the specific scoring guidelines. PL has prepared its own version of the TEMPS-50 scale with scoring guidelines included, along with the PL approach to diagnosis based on 75% cut-off on each scale as the strict definition, and 50% or higher cut-off as a broader definition. The scale is copyrighted by the Journal of Affective Disorders in the original publication, so for any commercial or broader use, that journal should be contacted for permission to use it.

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