Response to clozapine in psychosis associated with Velo-cardio-facial syndrome
DEAR EDITOR:
We report a case of new onset psychosis in a patient with velo-cardio-facial syndrome (VCFS) responsive only to clozapine but with adverse effects. This case highlights the increased sensitivity to clozapine in VCFS.
Case report. A 25-year-old woman with VCFS was admitted to the psychiatric unit after a one-week history of paranoid delusions, bizarre behavior, and auditory hallucinations. She believed coworkers were plotting against her, that they wanted to kill her, and that police agencies were looking for her. She had non-commanding auditory hallucinations of her boyfriend’s footsteps. She had no history of alcohol or substance abuse and no significant family psychiatric history. She had borderline mental retardation, narrow palpebral fissures, and mild orbital hypertelorism. The results of urine toxicology were negative, and a complete blood count, routine chemistry, transaminases, RPR, B12 level, folate level, and thyroid-stimulating hormone were all normal. A brain computed tomography (CT) scan showed developmental prominence of the lateral ventricles. Lower thoracic levoscolisosis and lumbar rotatory dextroscolisosis were seen on X-rays. During the hospitalization, trials of olanzapine, aripiprazole, ziprasidone, and perphenazine produced no improvement. The delusions and hallucinations persisted, and there were episodes of loud, angry outbursts. Clozapine was started at 25mg (daily dosage) and titrated by 25mg every one or two days. Within two weeks, despite mild sedation and hypersalivation, her mental status improved. She became less suspicious, denied hallucinations, and the outbursts abated. At 150mg clozapine, she had a grand-mal seizure. Within 30 minutes following the seizure, her prolactin level was measured and found to be 81.7ng/mL (normal 13–19ng/mL) and was found to be 13.3ng/mL the next day. Her electroencephalogram (EEG) showed no seizure activity. Clozapine was discontinued. Since she had responded to clozapine, a rechallenge commenced, beginning at 12.5mg and titrated up by 12.5mg every three days to 75mg. Divalproex sodium was added. After two weeks, the clozapine level was 172ng/mL and valproic acid level was 88.1mcg/mL. She showed no delusions, hallucinations, or outbursts. She was interactive, read books, played piano, and enjoyed drawing. She was discharged home with her family on clozapine 75mg and divalproex sodium 750mg.
Discussion. VCFS is a common genetic disorder estimated to affect 1 in 4000 births.[1] It is generally associated with deletion of chromosome 22q11.[2] The syndrome is characterized by distinctive dysmorphology, congenital heart disease, and learning disabilities.[3] After adolescence, a high prevalence of psychiatric illness is reported, including schizophrenia and bipolar disorders.[4] Psychosis in patients with VCFS is resistant to antipsychotic medications,[3] but partial response from risperidone and clozapine is reported.[2,4] One prior case reported clozapine improved psychotic symptoms but with adverse effects, including hypersalivation, constipation, and seizures.5 Our case confirms usefulness and reinforces caution in the use of clozapine in VCFS. Low dosage and slow titration of clozapine with divalproex resolved the psychosis in our patient without side effects. This case may assist management of psychosis in VCFS.
References
1. Murphy KC, Jones LA, Owen MJ. High rates of schizophrenia in adults with velo-cardio-facial syndrome. Arch General Psychiatry 1999;56:940–5.
2. Murphy KC. Annotation: Velo-cardio-facial syndrome. J Child Psychol Psychiatry 2005;46:563–71.
3. Vogels A, Verhoeven WMA, Tuinier S, et al. The psychopathological phenotype of velo-cardio-facial syndrome. Annales De Genetique.2002;45:89–95.
4. Gothelf D, Frisch A, Munitz H, et al. Clinical characteristics of schizophrenia associated with velo-cadio-facial syndrome. Schizophr Res 1999;35:105–12.
5. Galdston S, Clarke DJ. Clozapine treatment of psychosis with velo-cardio-facial syndrome. J Intellect Disabil Res 2005;49:567–70.
With regards,
Adeeb Yacoub, MD
Clinical Assistant Professor in Psychiatry, Stony Brook University Medical Center, Stony Brook, New York
Maria Aybar, MD
Third Year Psychiatric Resident, Stony Brook University Medical Center, Stony Brook, New York
Address for correspondence:
Adeeb Yacoub, MD, Stony Brook University Medical Center, HSC Level 10, Room 020, Stony Brook, NY 11794-8101; Phone (631) 444-2990; Fax: (631) 444-7534; E-mail: [email protected]
Regarding Catatonia
DEAR EDITOR:
Catatonia has been associated with a variety of illnesses, disturbances, and conditions. Consequently a variety of definitions have been applied to catatonia in clinical psychiatry and public understanding. We thank Bhati, et al., for their review of this topic in the March issue of Psychiatry 2007.[1]
The word catatonia is Greek for tension insanity. Kahlbaum developed the concept to describe a new illness. His description was later demoted to denote a subtype of psychiatric illness. Since that time, it has been excluded from routine clinical use but preserved in an exquisite and complex body of research and neuropsychiatric inquiry.[2]
Catatonia must be identified in the manner that it occurs in acute psychiatric units, emergency departments, chronic psychiatric units, intensive care units, nursing home settings, and outpatient clinics. The practical issue for clinicians is in determining if a patient has catatonia.[3,4] There is a practical value in this question because lorazepam and electroconvulsive therapy (ECT) can and do improve the patient’s response and outcome,[1] but would not be considered in many cases unless catatonia is identified. As evidence of the striking underdiagnosing of this syndrome, catatonia was identified in 18 percent of acute psychiatric patients using the Bush-Francis Catatonia Rating Scale (BFCRS),[5] yet diagnosed in only 1.8 percent of patients.[6] The barriers to ECT in our setting include the fact that the closest affiliated institution is 60 miles away and accepts only those patients who have failed multiple treatments and are significantly debilitated (e.g., not eating or drinking).
Consequently, we have used medications to treat patients with catatonia who were compromised but not so debilitated that they would be accepted in transfer for ECT. In an effort to identify other treatments, we performed a retrospective review of the literature associated with catatonia that included several authoritative texts and review articles on the subject of catatonia response. We divided drugs noted to be effective into their known classes and identified their mechanisms of action. This was then compared with the known pathophysiology and neurochemistry of catatonia. We also reviewed 49 cases that were rated with BFCRS as part of clinical care at a neuropsychiatric institution between 1995 and 2005. There was a cohort effect with standard antipsychotics used before 2000 and novel antipsychotics from 2000 to 2005. Thirty-five patients (66%) met the description of schizophrenia with catatonic features, but 10 patients (19%) had catatonia due to a general medical condition, which highlights the importance of this disorder in a medically ill population. Bipolar and unipolar affective disorders were found in four patients (9%). Some improvement in catatonia and function occurred with medication treatment in 16 of these 49 cases. This included second generation antipsychotics (2), clozapine (2), lorazepam (4), bromocriptine (1), memantine (adjunct) (6), and memantine (monotherapy) (1).
According to Northoff,[7] catatonia develops from GABAa hypoactivity, dopamine D2 hypoactivity, and glutamate NMDA hyperactivity or a combination of these. These diverse medications have been reported to help improve catatonia and in some cases worsen catatonia. While ECT is an effective treatment, it may not be available to all patients with catatonia. Catatonia is not a unitary syndrome, and there may be subtypes that respond favorably to one type of medication. Current clinical methods of identifying catatonia are insufficient, and the use of a rating scale, such as the BFCRS, is necessary. Lorazepam and other GABAa promoters (i.e., anticonvulsants) increase GABA activity as their mechanism of action.8 Clozapine and other novel antipsychotics have been reported to improve catatonia in psychosis, perhaps via a greater “pass-though” of dopamine to the D2 receptor. Perhaps the most promising finding is that NMDA antagonists (e.g., memantine and amantadine) may improve schizophrenia with catatonic features.[9]
REFERENCES
1. Bhati MT, Datto, CJ, O’Reardon JP. Clinical manifestations, diagnosis, and empirical treatments for catatonia. Psychiatry 2007;4(3):46–51.
2. Ungvari GS, Carroll B. Nosology of catatonia: From psychopathology to neurobiology. In: Caroff SN, Mann SC, Francis A, Fricchione GL (eds). Catatonia. Washington, DC: American Psychiatric Press, Inc., 2004.
3. Aboraya A, France C, Young J, et al. The validity of psychiatric diagnosis revisited: The clinician’s guide to improve the reliability of psychiatric diagnosis. Psychiatry 2005;2(9):48–56.
4. Aboraya A, Rankin E, France C,et al. The reliability of psychiatric diagnosis revisited: The clinician’s guide to improve the reliability of psychiatric diagnosis. Psychiatry 2006;3(1):41–50.
5. Bush G, Fink M, Petrides G, et al. Catatonia I: Rating scale and standardized examination. Acta Psychiatr Scand 1996;93:129–36.
6. van der Heijden FM, Tuinier S, Arts NJ, et al. Catatonia: Disappeared or under-diagnosed? Psychopathology 2005;38(1):3–8.
7. Northoff G. What catatonia can tell us about “top-down modulation”: A neuropsychiatric hypothesis. Behavior Brain Sci 2002; 25:555–604.
8. Rosebush PI, Hildebrand AM, Furlong BG, Mazurek M. Catatonic syndrome in a general psychiatric inpatient population: Frequency, clinical presentation, and response to lorazepam. J Clin Psychiatry 1990; 51:357–62.
9. Caroff S, Ungvari G. Catatonia. Psychiatr Ann 2007. In Press.
With regards,
Brendan T. Carroll, MD
Jose Ramirez, MD
Kishwer Faiz, PA-C, MBBS
Rob Kirkhart, PhD, PA-C
Christopher Thomas, PharmD
All from Marietta College, Chillicothe VA Medical Center, Chillicothe, Ohio
Address correspondence to:
Rob Kirkhart, PhD, PA-C, Clinical Professor Marietta College Chillicothe, VA Medical Center, 4155 Rowanne Rd., Columbus, OH 43214; Phone: (740) 773-1141 ext. 6599; Fax: (740) 772-7179; E-mail: [email protected]
Regarding Managing Erotic and eroticized transference
DEAR EDITOR:
In their article, “Recognizing and Managing Erotic and Eroticized Transferences” [Psychiatry 2007;4(4):47–50], Drs. Ladson and Welton should tell the readers whether their ideas apply to psychotherapy in general or only to psychotherapy methods derived from psychoanalytic theory.
With the exception of their single statement that does refer to “psychodynamically based psychotherapy,” Drs. Ladson and Welton refer generically to “psychotherapy,” or the even more vague “therapy,” as though the concepts of transference and countertransference are part of the terminology of all psychotherapies, when in fact they apply, at least as defined therein, only to psychotherapy methods derived from psychoanalytic theory. For example, the notion of transference is not used in cognitive behavioral or systemic psychotherapies.
No one would deny that patients and psychotherapists have feelings about each other regardless of the method of treatment. The need to judge whether such feelings are “irrationally intense” and then focus on “understanding” them as an essential component of the treatment, however, is peculiar to methods derived from psychoanalytic theory. The approach outlined by the authors to dealing with so-called “unrealistic” feelings may be considered irrelevant, impossible, or even counterproductive in other psychotherapies.
When authors discuss concepts peculiar to methods derived from psychoanalytic theory, they should refer to them as such either in the title, in the text, or both.
With regards,
H. Berryman Edwards, MD, FAPA
Bellevue, Washington
Regarding Psychiatric Evaluations of Asylum Seekers
Dear Editor:
I disagree with Dr. C.A. Morgan III’s opinion in the Psychiatry 2007 April issue, under Forensic Files, as expressed in the article, “Psychiatric evaluations of asylum seekers: Is it ethical practice or advocacy?” that doing forensic psychiatric evaluations on asylum seekers at the request of their attorneys is unethical. If Dr. Morgan’s arguments are used, forensic psychiatric evaluations in many other settings, too, would be unethical.
I have worked in the VA system for many years and have come across thousands of veterans and POWs from the World Wars, Korean Conflict, and Vietnam War diagnosed with posttraumatic stress disorder (PTSD), major depression, and other psychiatric disorders. In most of these cases, disabled veterans were given these diagnoses and awarded service connection and compensation checks based on history of exposure to trauma reported solely by them. If you use Dr. Morgan’s argument that a claimant’s reported exposure to trauma has to be objectively verified (presumably by an eyewitness), then most combat veterans would not be eligible for compensation since military records usually do not go beyond recording the presence of a soldier in a combat zone. The military records usually do not document the exact life-threatening trauma to which the soldier was exposed.
I once did a forensic psychiatric evaluation on a woman from an Islamic republic who converted from Islam to Christianity and was subjected to a lot of persecution, which resulted in development of PTSD. What is wrong with doing a psychiatric examination on such a person and making a diagnosis of PTSD, if DSM-IV criteria for PTSD are met, and then making a statement that history is obtained solely from the examinee and not verified by collateral sources?
I do not see doing psychiatric evaluations on asylum seeks, if done properly and ethically, as undermining the credibility of our profession. On the other hand, refusing to do psychiatric evaluations on asylum seeks, in my opinion, would be abdicating our professional responsibility.
With regards,
Chowallur Dev Chacko, MD, DFAPA
Distinguished Fellow of the American Psychiatric Association; Diplomate of the American Board of Psychiatry and Neurology; Board Certified in General, Addiction, and Forensic Psychiatry; Clinical Assistant Professor, USF College of Medicine; Courtesy Clinical Assistant Professor, UF College of Medicine; Past Chairman, Department of Psychiatry, Florida Hospital.
Author response
I would like to thank Dr. Chacko for his letter and thoughts. We are in agreement that statement history obtained solely from an examinee is not a valid basis for establishing a diagnosis of posttraumatic stress disorder (PTSD). Although I focused my comments on the asylum seeking process and did not link these to the challenges confronted by clinicians working within the VA system, I agree that clinicians who conduct VA disability evaluations are often confronted with the challenge of establishing a diagnosis of combat-related PTSD for which there is no objective evidence. The fact that clinicians perform such evaluations is not evidence that the process is a valid, evidence-based approach to the practice of psychiatry. Instead, it simply underscores the fact that well-meaning clinicians often support PTSD disability claims made by veterans without objective evidence.
As you may know, due to historical events (i.e., the destruction or loss of military records for many veterans) current VA disability rating board guidelines permit the board to err in favor of the veteran’s claim of PTSD when objective evidence about the veteran’s war-related index trauma is unavailable. This represents an administrative and political solution to the problem confronted by the VA, not the basis of evidence-based practice. I think it both unwise and unnecessary to replicate the difficulties confronted within the VA system when addressing complex issues of who is applying for citizenship in the US.
Sincerely,
C.A. Morgan, III, MD, MA
Associate Clinical Professor of Psychiatry, Yale University School of Medicine, National Center for Post Traumatic Stress Disorder, VA New England Healthcare System, West Haven, Connecticut.
