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Tardive Drug Effect Is Often Permanent

Ƶ MedicalToday

NEW ORLEANS -- Only about one patient in eight who develops tardive syndromes as a result of an antipsychotic or other drug therapy ever fully recovers, a researcher said here.

The recovery rate of 13% seen among 108 patients at Emory University's movement disorders clinic was lower than has previously been reported, said Deepti Zutshi, MD, of Emory, who presented results of the single-center study at the American Academy of Neurology's annual meeting.

Action Points

  • This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
  • A single-center retrospective study in a movement disorder clinic found that tardive syndromes today were most commonly caused by gastrointestinal neuroleptic drugs or atypical antipsychotics.
  • Note that the recovery rate in this study -- even with discontinuation of the offending drug, which occurred in all cases -- was very low at 13%, considerably lower than the approximately 30% reported in the literature.

Past estimates of recovery rates have been closer to 30%, she said.

Thus, Zutshi concluded, the findings "should emphasize the seriousness and permanency" of tardive syndromes -- also known as tardive dyskinesia -- and remind physicians to reserve drugs capable of causing them for approved, serious indications.

Tardive dyskinesia is a side effect of dopamine receptor blockers. The condition is usually associated with antipsychotic agents -- especially traditional ones like haloperidol (Haldol) and chlorpromazine (Thorazine).

Atypical antipsychotics are less prone to cause tardive syndromes but there is still a risk -- about 0.8% per year, according to Zutshi, versus up to 5.4% per year with traditional antipsychotics.

She and colleagues at Emory examined records of all patients diagnosed with tardive syndromes from 2006 to 2009. Patients included in the analysis had received a dopamine receptor blocker within four weeks of symptom onset and had at least one follow-up visit.

Because traditional antipsychotics are seldom used nowadays -- in large part because of the tardive dyskinesia risk -- only 7% of the cases involved such drugs. Atypical antipsychotics accounted for 36%. One patient's symptoms were attributed to an SSRI antidepressant, and 14% had been exposed to at least two potentially offending drug types.

But the single largest likely cause of symptoms was gastrointestinal neuroleptic drugs, accounting for 42% of cases. Metoclopramide was involved in an overwhelming majority of these cases (87%), Zutshi reported.

About two-thirds of patients were women and the mean age for cases was 59. Clinical diagnoses prompting the dopamine blocker treatment closely paralleled the drugs used -- 44% were mood or psychotic disorders and 41% were for gastrointestinal complaints.

Patients had been taking the drugs for mean of 4.8 years (SD 5.6). From the start of therapy to first development of abnormal movements, the mean was 3.7 years (SD 5.6).

All patients had stopped taking the dopamine blockers by the time they were seen in the Emory clinic, which made the study unique among reports of tardive dyskinesia outcomes, Zutshi said.

The specific tardive symptoms varied considerably. About two-thirds had no extrapyramidal symptoms. Approximately one-quarter had orofacial and generalized dyskinesia and 12% had orofacial and generalized dystonia, but half of patients showed a mixed presentation.

With a mean followup of about 3 years, symptoms had cleared up in 14 of the 108 patients, Zutshi reported. She and her colleagues could not find any factors associated with greater likelihood of recovery.

Duration of total drug exposure or the duration of exposure before symptoms developed were both the same in those who recovered versus those who didn't. Nor did the class of drug, the primary diagnosis, patient age, nor history of diabetes or alcohol abuse differ between the groups.

Another notable finding was that symptoms generally worsened in patients initially seen with mild symptoms, but grew less severe in those with moderate or severe symptoms at the first evaluation.

Zutshi cited several limitations of the study, including its retrospective, single-center design and the small numbers of patients in some categories.

Also, she said, some patients in whom tardive symptoms had resolved might have never returned to the clinic. Since only patients with follow-up were included, the 13% recovery rate could be a significant underestimate.

Disclosures

The study had no external funding.

Zutshi reported no potential conflicts of interest.

Primary Source

American Academy of Neurology

Zutshi D, et al "Reversibility of tardive syndromes" AAN 2012; Abstract P04.031.