LAS VEGAS – Differences in drug responses probably offer the strongest evidence that bipolar disorder and schizophrenia may be separate entities, according to Dr. Charles B. Nemeroff.
The notion that the two are different manifestations of the same disease has gained traction in some quarters because, at least superficially, the two illnesses have quite a bit in common, including age of onset, response to atypical antipsychotics, ventricular enlargement, and shared genetic characteristics.
Dr. Charles B. Nemeroff
Early childhood abuse and neglect can increase the risk of both in vulnerable people, as well, and bipolar disorder patients can have auditory hallucinations and paranoid delusions, just as those with schizophrenia do, Dr. Nemeroff said at the Nevada Psychiatric Association’s annual psychopharmacology update.
Indeed, the possibility that they are even on the same spectrum has "implications in terms of current treatment and treatment development," but Dr. Nemeroff said he has his doubts. "The last chapter to this debate has not yet been written," he said.
That both respond to atypicals could be a red herring, for instance. "Imipramine is effective for treating both depression and enuresis, but I don’t think they’re the same thing," said Dr. Nemeroff, Leonard M. Miller Professor and chairman of the department of psychiatry and behavioral sciences at the University of Miami.
Regarding genes, some indeed are associated with both schizophrenia and bipolar disorder, but others appear to increase risk for one but not the other. Overall, genes account for about two-thirds of the risk for bipolar disorder, but only about half the risk for schizophrenia, he said (Neurosci. Biobehav. Rev. 2012;36:556-71).
Bipolar patients also do not lose brain volume over time, unlike patients with schizophrenia, and they often report an early onset of depression, sometimes before puberty. "We often don’t hear that in patients with schizophrenia, even when you talk to family members. There may have been something [odd] going on in those early years, but it doesn’t look like early-onset depression," he said.
Atypicals aside, differences in drug responses probably offer the strongest evidence that the two illnesses are separate entities.
Although of great help in manic patients, anticonvulsants "have no efficacy whatsoever in schizophrenia." Likewise, antidepressants can "rocket" bipolar patients into mania, but "have you ever seen a schizophrenic patient given an antidepressant become acutely manic? I haven’t," Dr. Nemeroff said.
Perhaps the response to lithium is the most telling of all. It remains one of the most effective treatments for bipolar disorder but "just does not work" for schizophrenia, according to numerous trials as both monotherapy and add-on therapy, he said.
"I’ve seen dozens of [bipolar] patients" struggle for years despite treatment with newer agents, but who have never had a lithium trial. When it’s finally tried, they often have "phenomenal response[s]. They became euthymic and remain euthymic for years, and never suffer an episode. I’ve rarely ever seen that with any other treatment for bipolar disorder. [Lithium is] a great drug; it’s also cheap," he said. "Cheap is good for our patients."
Lithium is underused because "nobody’s marketing it to you," he said.
Ongoing monitoring for kidney, thyroid, and other side effects probably puts some psychiatrists off, as well, but it’s really not any more complicated than the ongoing monitoring needed with atypicals and anticonvulsants, he said.
Plus, "there’s pretty good data that if you check TSH [thyroid-stimulating hormone] every 6 months, you’ll be able to catch any incipient hyperthyroidism. Patients who have [thyroid] antibodies at baseline are generally the ones who go on to develop thyroid problems, so you can check that at baseline," he said.
For patients with refractory bipolar depression, "my favorite combination has been lamotrigine and MAO inhibitors," particularly tranylcypromine. "I’ve probably gotten more people [out of] bipolar depression with that – after they’ve been marinated in everything else – than any other strategy besides [electroconvulsive therapy]."
And "lamotrigine doesn’t work in patients with schizophrenia," he noted.
Dr. Nemeroff reported stock ownership, consultant fees, or other income from Allergan, Lilly, Shire, Roche, NovaDel Pharma, BioPharma, AstraZeneca, and other companies.