Welcome to My Pitch Universe: Carbamazepine, Aripiprazole, and Pharmacological Pitch-Bending

H aving perfect pitch, I find listening to these [Baroque historically-informed] performances very jarring. Even when I put in Podger’s recording of Bach I had to really adjust. I can’t listen to Quarta’s Paganini 1, which is tuned up. It’s just too strange.”
  — Pieter Viljoen, 04-DEC-2006.

This wouldn’t likely be noticed by anybody who doesn’t have ‘perfect pitch’ [‘absolute pitch’]. But she was triply gifted—with perfect pitch, mild autism, and epilepsy. Having ‘absolute pitch’ was sometimes helpful—in sight-reading, for example, or a capella singing or improvising jazz. But most of the time it was a nuisance. It was especially disturbing to her to tune her violin to A415 Hz or other Baroque tunings.

Perfect pitch [also called ‘absolute pitch’] is the ability to hear a particular note (or chord) and know, without any instrument or other pitch reference, which note it is. Compare this to ‘relative pitch’, which is the ability to hear the difference in pitch between a note and a given reference (musical interval). Most people have relative pitch to some degree, but perfect pitch only occurs in about 1 per 10,000 people. Here’s how it works: I’d wake her up at 3 a.m., sing some note of my choice, and she could tell you right away that I sang A above middle-C, and I sang it flat, about 427 Hz she thought.

So she was chronically on aripiprazole (Abilify™) for her autism, and then her doctor switched her from her regular anticonvulsant medication to carbamazepine (Tegretol™).

The first two days after the Tegretol was added to the Abilify, she yelled about the piano. Said it was horrifically out of tune. Asked whether I had done something despicable to the thermostat.

Within a few days after she started taking the Tegretol, when she played the piano she felt as if each note was a half-step lower than its position on the keyboard. The notes were consonant with her internal pitch-universe, just transposed down a half-step. During that period, if you woke her up at 3 a.m. and sang your note she would tell you that it was G# above middle-C and you are flat, about 412 Hz. At that time she was taking 15 mg per day of the Abilify and 200 mg twice per day of the Tegretol. She complained that modern recordings sounded to her like the musicians were using Baroque tuning. It was disorienting—like people were trying to play ‘tricks’ on her.

And then two seizures happened in one week—so the doctor bumped the Tegretol dose up to 400 mg twice per day. Within three days each note sounded to her like it was a half-step plus a quarter-tone lower than its position on the keyboard. You woke her up at 3 a.m. and sang your note and she told you that it was G above middle-C and way-sharp, hideous, about 404 Hz. She looked at her digital tuning meter in utter disbelief. She refused to listen to certain CDs, claimed that there must be something wrong with the CD player. Said she was being sucked into a ‘black hole’, that ‘gravity’ was pulling on her mind. Hated it.

Then she developed a skin condition, ‘toxic epidermal necrolysis’ (TEN), and the doc took her off the Tegretol and switched her to lamotrigine (Lamictal™). After about 3 days following the discontinuation of the Tegretol, she said I was singing G# again. Then, a week later, she said I was singing an A, slightly flat, like I used to do. We were back in the same universe.

The neurologists, naturally, were oblivious to all of this. None of them had any familiarity with the accumulating evidence of a carbamazepine-activated effect on the peripheral auditory system, which increases the sensitivity to low-pitched sounds and causes the altered pitch perceptions. We only found out about that ourselves, by searching around on PubMed and elsewhere on the web.

Most of the journal articles and scientific reports say that musical performances by people with perfect pitch who are on carbamazepine are heard as a semitone lower than they are in actuality. The condition is probably a lot more common than the occasional case-reports would suggest. If my friend had not been able to discern absolute pitch, she would’ve been unable to detect a lowered pitch perception.

Functional MRI (fMRI) imaging of the structure in the brain called the planum temporale shows asymmetries that are associated with perfect pitch, but no fMRI to-date have been performed on people with perfect pitch who are on carbamazepine.


Most of the medical literature reports of pharmacologically-induced pitch-bending involve Tegretol by itself. I can’t find any reports that involve two or more anticonvulsant medications. I can’t find any reports that involve a drug used for autism-spectrum disorders, like Abilify. I can’t find any reports that involve Abilify with an SSRI or other antidepressant.

And even the case-reports for Tegretol don’t really address the dose-ranging aspect. When you go from 10 mg/kg/24h up to 35 mg/kg/24h (to 1600 mg/24h, say), for example. None of the reports addresses dose-escalation related pitch-bending, like what my friend had.

Probably the most comfort we got came from the recent paper in the Proceedings of the National Academy of Sciences (PNAS) last Fall, from the UCSF team who’ve been conducting a large study of absolute pitch for several years. Helped us, at least, to know how ‘not alone’ we are.


Side-effects may include dizziness, drowsiness, disturbances of coordination, confusion, headache, fatigue, blurred vision, visual hallucinations, transient diplopia, oculomotor disturbances, nystagmus, speech disturbances, abnormal involuntary movements, peripheral neuritis and paresthesias, depression with agitation, talkativeness, tinnitus, and hyperacusis. ‘Hyperacusis’. Oh, yeah. You who write these drug package-inserts, you have no idea. No. Idea.

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• Univ California San Francisco Absolute Pitch Study
  
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• PerfectPitch.com [expensive ear-training CD-ROM course]
  
• Violinist.com post on absolute pitch and early music tunings (A 415 Hz)
  
• Absolute Pitch Education forum
  
• Perfect Pitch Illness blog on Myspace
  
• John Petrucci thread on perfect pitch