Case 2: Psychosis with bipolar mania

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Dr Joseph Goldberg: We’ll call this patient Mr. S. He’s a 20-year-old single white male undergraduate on medical leave from his freshman year in college, who’s being admitted for his second lifetime hospitalization with acute psychosis. His chief complaint was “the timberline means death”. I caused it. Other people are suffering and it is my fault His roommate noted that he was often awake at night writing out lengthy obscure essays about humanity on his computer, not eating, and drinking only coffee and beer. He also began visiting online gambling sites, and in the month prior to admission had lost about $4000 playing Texas Hold ‘Em on the Internet. His parents had come to his dormitory after he had not returned their telephone calls for over a week. They called his psychiatrist at home, my predecessor, Dr. H, whom he had not seen since leaving again for college three months earlier in the fall semester. That psychiatrist advised bringing him to the emergency department of the local university medical center. Dr. H diagnosed him a year earlier with attention deficit disorder and depression and treated him—this is based on his self report of trouble concentrating and prescribed Adderall XR 20 milligrams a day with Lexapro 20 milligrams a day. At the time that his parents came to see him in his dorm now, they noted that he had a full bottle of Lexapro unopened, unused, but had an empty bottle of Adderall in the dorm room.

They brought him to the emergency department, and there the patient expressed intense concerns that al-Qaeda was infiltrating the Internet and had chosen him as a military operative. He perceived secret messages being sent to him from tree stumps, and believed that the patterns in which they had been cut down imparted clues about future terrorist attacks. He believed that he played some critical role in national security and was responsible for the 9/11 attacks and blames himself for death and suffering. He said he stopped taking Lexapro a while ago because it had caused weight gain and sexual side effects. He denied currently feeling depressed or euphoric and denied suicidal thoughts or hallucinations.

In terms of his past psychiatric history, he first came to attention in his junior year of high school at age 16 when he briefly saw a therapist in the context of poor grades and what was termed moodiness.

At age 19 soon after starting college, he was hospitalized after trying to jump off a building after getting drunk at a party. That event led to his returning home to live with his parents, and he was placed on a medical disability for the remainder of what would have originally been his freshman year. Family history is notable for an older brother who had been hospitalized and diagnosed with bipolar disorder who completed suicide at age 28. His father has had recurrent episodes of depression, treated with various anti-depressants, and his mother has panic disorder, which has been treated with SSRIs and benzodiazepines. With regard to his social history, it was an uneventful birth and early development period. He was considered a popular child with many friends. While growing up excelled in school, especially math and science, until an inexplicable decline in his school performance during his junior year, as mentioned above, in high school. He denied ever having had any romantic or sexual relationships. On his mental status exam, he is a moderately overweight man with unkempt greasy long hair, appearing somewhat disheveled, with several days’ beard growth.

In the interview, he was at times motorically retarded, and at other times excessively animated. He made poor eye contact and occasionally seemed internally preoccupied, but was also easily distracted by background noises in the exam room. He spoke in staccato rapid-fire sentences in response to questions, and was often difficult to interrupt. He described his mood as calm and mellow, but his affect was dysphoric. His thought processes were at times tangential, circumstantial and illogical. His thought content was notable for paranoid delusions, grandiose delusions, and ideas of reference. He denied hallucinations, suicidal thoughts or homicidal thoughts, and further assessment; his cognitive functioning was limited because of his thought disorder and distractibility. He had grossly impaired insight in judgment. Lab testing in the ER was notable only for a tox screen positive for amphetamine, which was consistent with the Adderall use.

Working diagnoses were axis one bipolar disorder mixed episode with psychotic features with rule out diagnoses of amphetamine induced psychosis, a ruling out of paranoid schizophrenia, and a ruling out of schizophasic disorder bipolar subtype. He was hospitalized, and begun on Divalproex per the PDR, 750 milligrams a day and begun on resperital and resparidone, one milligram twice daily. His psychosis persisted and therefore the resparidone was gradually increased to four milligrams twice daily with an addition of benztropine, two milligrams at night for acathesia. The Divalproex was fully increased to 1500 milligrams a day with a valproate level of 74 micrograms per deciliter. He was modestly improved.

Discharged from the hospital, went to an intensive outpatient program, and in that setting, he very soon appeared grossly psychotic, couldn’t follow instructions, and was re-hospitalized. Divalproex was increased further to 2000 milligrams a day with a serum level of 96 micrograms per deciliter, and the determination was made that the Resparidone was lacking in adequate efficacy, so it was therefore cross-tapered to olanzapine. With that, olanzapine dosing was increased gradually to 40 milligrams a day. He had a marked reduction in his agitation, and the overt signs of psychosis, within one week. Then he was discharged and resumed at the IOP. Had a follow-up appointment with me about a month after this. He denied any psychotic symptoms but appeared sullen, depressed; spending much time in bed, and in that month had gained close to 20 pounds. He and his parents both were please by the improvement in the psychotic symptoms, but they were now concerned about his depression and very real on the concern about the marked weight gain, so their question, when I last saw them, was, “Well, can we stop his medicines now?”

Dr Henry Nasrallah: I was appalled by the misdiagnosis of Dr. H given that the many personal and family clues that this is a bipolar disorder and obviously whenever you have a wrong diagnosis, you embark on therapeutic misadventures, and he gave him what you know a kid like this with what looks like the onset of a bipolar disorder the worst possible combination of a stimulant and an antidepressant, which in my judgment could very well have contributed to his deterioration and exacerbation of his symptoms. And Joe, could you tell us what you think was the reason that this patient failed to respond well to the combination of risperidal and valproate and seems to deteriorate rapidly after discharge.

Dr Joseph Goldberg: I think the stimulant use sure didn’t help. With respect to the divalproate I agree if someone is floridly ill and I think if you look at the Michael Allen study and the “Medical Journal” and doses with the ER in acute mania. I think levels more in the 90-range are probably better …

Dr Henry Nasrallah: More than 95 even.

Dr Joseph Goldberg: I do not start the floridly ill manic patients on 750 milligrams of valproate unless there’s a very compelling reason to do it, so even though the PDR speaks to that. I think you know with the risperidone, it’s interesting. He was on eight milligrams a day, and had extrapyramidal side effects and had stigmata of you know taking the medication, and was somewhat better but I think with the loss of structure and support from the hospital. I think he’d just decompensated, and my sense was that if we call eight milligrams a day of risperidone an adequate trial. But I think the sense was this was not a broad spectrum, enough agent for him. I end up choosing olanzapine, at least in the short run, because of my perception that it would probably be a better choice after a non-response to another typical antipsychotic.

And indeed, as it did seem to stabilize his mania and psychosis with a somewhat higher valproate dose, but you know now the sticking point is several-fold. He is in a post manic depression, which the valproate and olanzapine is not sufficiently treating. He’s gained a tremendous amount of weight and the likelihood of much more substantial weight gain down the road if he were to stay on this is fairly high.

Dr Steven Pariser: Eighteen pounds in a month is in my view a clear mandate that something be done you know with the atypical agent, and also could include a need for sleep study, because if that's a component to this, and he does better with a CPAP machine, it may make a considerable difference in his depression, and also in his ability to lose weight.

Dr Henry Nasrallah: Yes, I also want to add another kind of option that occurred to me. If this patient needed about 40 milligrams of olanzapine, that's twice the upper limit of the package insert. Why not use another atypical that is also very effective in psychosis and mania as well as depression? Quetiapine is an atypical, if used at the same proportionate dose as olanzapine 40, it would be about 1,600 to 2,000. And I have used those high doses in very difficult cases with good results that you don't get at the usual doses of 800 of quetiapine, just like maybe 20 of olanzapine didn't seem to work in this patient.

Dr Donald Black: Yes, Henry, this is Don Black; I actually have a paper in front of me by Gupta, et. al. from schizophrenia research in 2004, showing that when patients were switched from Alanzapine to Clothiapine, they actually lost weight.

Dr Henry Nasrallah: Sure.

Dr Donald Black: So you could accomplish some weight loss through that strategy, plus the other advantages that that drug has for me, that would be the sedating properties, since sleep is such a problem with this individual.

Dr Henry Nasrallah: With the history of suicide—completed suicide in a brother. I would aggressively watch his depressive symptoms, and maybe proactively give him drugs that prevent suicidality. Again, for a patient like this psychotic, bipolar mixed features, I would consider only two options for that, either clozapine which of course would exacerbate his metabolic syndrome. Unfortunately but it is—it does help the mania and the suicidality, but also quetiapine, which is approved for bipolar depression, and there are no specific indications for suicidality, but certainly by reducing their depressive features in a bipolar patient, you minimize the risk for suicide.

Dr Donald Black: Now there's another issue, and I hate to bring this up, it's called defensive medicine. But if someone has bipolar depression, it certainly is a consideration to use an agent that does have an indication for bipolar depression. So using quetiapine or perhaps aripiprazole although it has a unipolar augmentation approval probably makes sense in a variety of other ways that are protective. I should say forensically protective perhaps. I ended up putting him on Topamax to see if I could make some inroads with the weight, keep him with buy-in into the treatment, And then also the depression, so actually there are two things I added to topiramate for the weight gain and lamotrigine, which is not as robust as we thought it was a few years ago, but I added it to see if we might help to get some additional benefit.