Drug review: clomipramine (Anafranil)

Generally amphetamine helps with OCD-spectrum symptoms (an advantage to which relatively few mental healthcare providers avail their patients), but it has an unfortunate tendency to encourage skin picking and other “body focused repetitive disorders” for some people. It turns out I’m one of those people, so I asked my psychiatrist what he recommended.

Before I reveal his suggestion, I feel the need to go off on a particular tangent. You see, I could spend all the hours of the day studying psychiatry – delving into its history, poring over its arcane trivia, hypothesizing, cooking up experiments. But I can hardly imagine a more loathsome fate than that of becoming a clinical psychiatrist, because what could sap the excitement and joy from a subject as quickly or thoroughly as the Hippocratic oath? A profession which advertises a prohibition against risk-taking as its central tenet is one that values stability over progress, bureaucracy over creativity. And when your field’s knowledge base is as underdeveloped as psychiatry’s is, you can’t really afford stagnation.

So he suggested Lexapro, an SSRI. Boring. I floated the idea of trying a tricyclic antidepressant instead. TCAs comprised the second generation of antidepressants, following the MAOIs, and were in use from the 1960s until the institution of our Great SSRI Overlords in the 90s. The folk wisdom in psychiatric circles is that there’s a negative correlation between an antidepressant’s age and its efficacy, but rather inconveniently a positive one with its deadliness, and it was decided that providing depressed patients with a potential means to commit suicide wasn’t very sensible. Now the TCAs and MAOIs were left to gather dust in the backrooms of pharmacies as second- and third-line options for treatment-resistant depression, while all the doctors went and swore fealty to their new master, fluoxetine. Yet still they knew, in their heart of hearts, that the ways of old truly possessed superior efficacy and diminished sexual and metabolic side effects.

I selected clomipramine on the basis of its reputation for OCD and its position as number three on the official SSC list of things you should try instead of whatever your doctor recommends. It’s supposed to be milder than its parent, imipramine, but the lowest dose commercially available (at 25 mg per capsule) is still subjectively pretty striking. The most immediately noticeable effect was on my sleep, as it woke me the first couple of nights after four dreamless hours, and the next couple after six. Despite this, I felt not only well but happy, a rare occurrence first thing in the morning even with adequate sleep. I concluded that the loss of the REM-heavy tail end of my sleep was likely due to the well-known fact that serotonergic drugs inhibit REM, a sleep stage that is generally disordered in the clinically depressed, and which incidentally has various theories attached to it implicating it in depression’s pathogenesis. On several occasions I fell asleep before taking my nightly dose, and on all of these I slept for exceptionally long periods of time and had exceptionally vivid and memorable dreams – “rebound REM”.

The other very robust effect was a reduction in hyperactivity and impulsivity, possibly larger than with stimulant treatment. When I was much younger I was able to read for many hours on end, and I lost this ability sometime in adolescence. I could force myself to read while on amphetamine, with frequent endogenous and exogenous interrupts. But clomipramine seems to allow me to get completely absorbed into things, rather than having to refocus my ever-errant attention back on them continually, making extended reading sessions not only possible but enjoyable. And I suspect that this quality of absorption is related to my subjective sense of the world having more “color” and “meaning”, and possibly to the fact that my initial impression of this drug was that it felt like a very low dose of MDMA. The dark side of absorption is that I have had a couple of panic attacks in the last month, one understandably after fainting for the first time ever, the other somewhat less so after a plausible but still overblown serotonin syndrome scare, both of which resulted in unnecessary (and unusual) usage of emergency medical services.

Apart from those few isolated incidents, background anxiety has been down, and my frustration threshold has raised significantly. More surprisingly, I’ve found that unpleasant sensory sensitivities are mitigated to the extent of allowing me to work to music for the first time ever, and to wear my hair down without constant aggravated fiddling to prevent it from touching my skin or pulling at my scalp. And my improved mood has caused my sociability to soar from Emily Dickinson levels to near-JD Salinger heights.

The least noticeable effect was on the very thing I requested the drug for, skin-picking, but considering all the incidental benefits, I can’t muster up too much disappointment. I’ve been on it a month, and overall I’d say I’m pretty sold on clomipramine. Having heard from a lot of people put on SSRIs or SNRIs who weren’t sure whether or when their drugs did something, I can wholeheartedly recommend clomipramine as a drug that definitely does something, even if it’s not the thing you expected or necessarily wanted. But all those little surprises are what make psychopharmacology so fun, aren’t they?

Find more nuggets of pharmacological knowledge on clomipramine and the TCAs here.

Update: It looks like I failed to mention this before, but clomipramine is an anticholinergic. Acetylcholine is a rather important neurotransmitter that does things like initiate REM sleep (I’m unsure of whether clomipramine’s anticholinergic effect is great enough to make a noticeable dent here), and chronic antagonism tends to impair learning and memory, and could be associated with dementia. I suppose one could try pairing a cholinesterase inhibitor with it, but racetams are more common, and I’ve started taking a noopept/choline complex now and again that seems to perk me up.


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