Case 1: Treatment-resistant psychosis and schizophrenia

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Dr Donald Black: Michael is a 54-year-old divorced white male with chronic schizophrenia who presented to our emergency department seeking protection from is mother, who he believed was planning to kill him. He believes that she had seduced him as a young child. His treating psychiatrist was contacted and confirmed that Michael was enrolled in an assertive community treatment program. The nurse had visited the patient earlier that day and felt he was more paranoid and disorganized than was typical, and encouraged him to enter the hospital. He was receiving both haloperidol and risperdal injections to control the schizophrenia but had refused the shots scheduled for 10 days earlier. He had developed schizophrenia at age 17 and had been psychiatrically hospitalized more than three dozen times, probably more like 50 or 60 times. Frequently hostile, Michael had never been assaultive until earlier this year when, while hospitalized, he assaulted a nurse who he believed was planning on harming him. The illness was not disabling during its first five years, and Michael was able to attend college, receiving his BA in comparative literature. Afterwards, he was never able to hold gainful employment and was eventually given social security disability benefits. His target symptoms include disorganized thinking, tangential speech, paranoid and sexual delusions, auditory hallucinations, and hostility. He lived in his own apartment but had refused nursing home or rather residential placement. His parents had always monitored his welfare and visited him several times each week, helping Michael by cleaning his apartment, doing laundry, and bringing food.

He had received both conventional and atypical anti-psychotic medications over the years with only modest benefit because of poor compliance. Michael is now required through a mental health commitment to receive injections. He takes haloperidol, decanoid, 100 milligrams monthly, and risperdal, decanoid, 25 milligrams every other week. He occasionally develops depressive symptoms and has threatened to kill himself, but anti-depressants have not led to consistent improvement, and he is not currently taking them. Though he has a heavy cigarette smoking habit, he does not drink or use illicit drugs. Other than his immediate family, all of whom are high functioning and psychiatrically well, he socializes exclusively with his ex-wife. Michael has developed tardive dyskinesia from his anti-psychotic medications and displayed mild pseudo-Parkinsonism. And other than a cough related to his heavy smoking, he had no physical complaint.

On admission to the hospital, he was seen in the emergency department lying on a gurney. He was unshaven, had long greasy hair, and was smelly. His clothes were dirty and mismatched, and despite the warm summer weather, he wore multiple layers of clothing. He displayed an angry and hostile affect, and directed anger at his mother, who he accused of sexually molesting him in childhood. He was sexually preoccupied and indicated that one reason he came in was because he couldn't get it up. Just like the protagonist in Hemingway's “The Sun Also Rises”. He has prominent oral buckle movements, which he appears unaware of, and has mild hand tremors and cog wheel rigidity. He has no insight, though understood that the doctors believe he has schizophrenia. He cooperated well with the inpatient team, and though disorganized in his behavior and speech and mildly agitated, agreed to take his injections. The outpatient mental health commitment requires him to take medication and he understood that he would not be discharged unless he agreed to take it. That said, he believes he has been illegally committed and that his mother is behind the plot, He was discharged the next day, and the acts program was informed that he needed close monitoring.

So the outcome of this is that while he had taken his medication, he remained chronic and refractory and because of his lack of insight cannot be trusted to take oral medications, so we're essentially forced to give him medication by injection. He functioned better when taking clozapine, but he eventually discontinued that and refused to restart because of the inconvenience and discomfort of weekly blood draws. Neither haloperidol nor risperdal injections alone sufficiently controlled the illness, though the two combined appeared to the act team to provide better than - better results than either agent alone, though his treating psychiatrist understands that the combination is not evidence based. While Michael complained about the pseudo-Parkinsonism, currently managed with trihexyphenidyl, five milligrams twice daily, the tardive dyskinesia went unnoticed.

Dr Henry Nasrallah: Although he sounds like a chronic schizophrenic, I still cannot shake off the possibility that he is a severe psychotic bipolar, and the reason for that is the relatively better initial functioning for five years after the illness and achieving a college degree, and also the presence of both depression and suicidal ideas and threats as well as highly irritable mood and also assaultiveness.

Dr Donald Black: Yes. I agree. It's not-his diagnosis has never been entirely clear.

Dr Joseph Goldberg: I would imagine he's been tried on mood stabilizers even as adjuncts to the neuroleptics over the years. One question I'd have is historically what the response there has been, and then secondly, regardless of diagnosis and the present whether or not Depakote was considered or tried as an adjunct for the agitation in the present.

Dr Donald Black: He has been on Depakote and other mood stabilizers periodically. He's taken most all of them, the lithium, early on, carbamazepine, Depakote, and it's unclear from the records or my clinical impression how much he benefits from them.

Dr Steven Pariser: One of the pitfalls, mouse traps, of dealing with very refractory patients is that they wear on us as clinicians and fatigue us, and almost all the refractory patients that I see have been on everything. I sometimes start all over again because it's just too easy to get fatigued. We would image him, and we would also make sure that we had assessed all of the appropriate metabolic profiles, including vitamin levels you know I'm sure you've done this, syphilis screens, everything.

Dr Donald Black: Now one of the things they did tell me is that he really dislikes his pseudo-Parkinsonism and so he's constantly pestering them about reducing his haldol dose, so they had reduced it, I believe it's at a hundred now per month, and they reduced it, because he wanted them to, to 75 per month, and so his clinical deterioration really seemed to follow that, and then it accelerated when he refused his injection schedule about 10 days before he actually came in.

Dr Henry Nasrallah: He seems to have erectile dysfunction, which is not surprising given that both risperdal and haloperidol would do that in males. The reason I mentioned it is it might be an incentive for him to talk him into taking clozapine again. Clozapine already helped him, as you said, and even if he is a psychotic bipolar, clozapine has been shown to be the only medication that really is consistently has efficacy in treatment refractory bipolar patients, amenia or even depression at times. But that - the fact that he has blood draws you know makes me wonder whether you could do it with a nasal stick to check his white blood count every week, make it easier for him. His tardive dyskinesia is also interesting in that bipolar patients are much more prone to EDS, which he has, as with tardive dyskinesia which he has.

So I would suggest that he be either switched to clozapine partially. I would keep him on the risperdal and remove the haldol, and I would increase risperdal. It's already, in my opinion, insufficient. I} would use that as an insurance policy because of his compliance issue, and then add a small dose of clozapine, maybe a couple of hundred. I think his symptoms would improve and maybe his EPS would also go away since the acute EPS symptoms and the erectile dysfunction.

Dr Donald Black: Well, I think that's worth pursuing. it's about time that he enter some kind of care facility because he truly is not able to care for himself. But he absolutely refuses to do that. I believe if he was in a care facility, we-and the nurses could administer oral drugs every-to him, he'd probably cooperate with that and would be improved.

Dr Joseph Goldberg: When I encounter people like this who've been on just about everything, if not everything, I always figure like well, what are the treatment goals? The treatment goals may have less to do with trying to modify disease course and affect anybody's fundamental change from things like you know basis fundamental safety. I'd worry about his suicide risk, not today, but over the next several years.

Dr Henry Nasrallah: Well, we need to wrap up this case with having really picked up on a lot of interesting aspects of this case and we can probably talk about it a lot more. But I would like to again emphasize my point of view that clozapine would be the only thing we can try in a very refractory patient like this, not only for his psychotic symptoms but also remember clozapine is the only drug approved for suicidality in schizophrenia, if he is schizophrenic, and may help his refractory mania if he's manic.

But I agree with Dr. Pariser about ruling out frontal temporal dementia. I agree with Dr. Goldberg about looking at you know para pharmacological issues like safety, suicidality. I agree with Don Black about putting him in an environment where he is monitored more consistently. So there are several options we can follow after this patient.