Jon McClellanIt is Standard Practice to prescribe neuroleptic, called "antipsychotic," and other psychiatric drugs which have not been approved for pediatric use, that is, not tested for safety and/or efficacy in children and adolescents. The reason it is a standard practice is because Treatment Protocols and Practice Parameters and treatment algorithms written by Jon McClellan and other child and adolescent psychiatrists recommend prescribing the teratogenic drugs for children's behavioral problems, and for virtually every psychiatric diagnosis given to children and teens---there have even been reports the drugs are prescribed absent any psychiatric diagnosis...
What really gets me about this 'doctor' is considered a lead researcher, 'an authority' who actually wrote the book, so to speak, on prescribing teratogenic drugs to kids, yet he claimed in a Senate Hearing under oath that he had no insight into why it has become a "Standard Practice!" Jon McClellan's failure to comply with or conform to Ethical Guidelines and Legal Standards when he 'treated' my son, should have cost him his license to practice medicine. This 'doctor,' as an agent working for the State of Washington, violated every single Ethical and Legal parameter applicable to the practice of medicine and bio-medical research involving human subjects, he used my son like a lab animal without regard to his human dignity; without obtaining the proper consent, and over my vehement protests. This 'doctor' claimed in a Senate Hearing to have no insight into how the teratogenic drugs he recommends in his professional writing and that he advises other professionals how to prescribe off-label, came to be widely prescribed to children and adolescents without the empirical data necessary to or support prescribing the drugs as a medical treatment at all,
Jon McClellan's callous disregard for the deleterious effects of the drugs on my son was horrifying for a mother to witness; his utter lack empathy and compassion were devastating, as was the lack of accountability or responsibility for further traumatizing and ultimately disabling my once brilliant son.
Jon McClellan has ample experience prescribing psychotropic drugs off-label over the last couple of decades. He has taught students at the University of Washington, and advises other medical professionals in phone consultations in a program that Washington State implemented. In spite of these facts, and a professional career over 2 + decades, he claims to have no insight whatsoever into the prescribing practices he uses and recommends to others. Prescribing practices which have defrauded taxpayers through the Medicaid program. Worse than the decimated budgets and robbing of the American taxpayers, is the plight of the primary victims of this psychiatric practice: the children whose lives have been forever altered, like my son's has been; and the children whose lives have been lost: like Rebecca Riley and Gabriel Meyers.
Does anyone really believe Jon McClellan has absolutely no insight into the reason this investigation is needed? Does anybody wonder what happens to doctors who prescribe drugs off-label, and ultimately cause a child's death? The doctor that "treated" Gabriel Meyer to death, got a "warning letter" and still has a medical license to practice medicine. The doctor that "treated" Rebecca Riley to death was granted immunity for testifying against her mother at trial. As usual, Jon McClellan was quoted in the press when these events occurred: This expert who claims he has NO IDEA why these drugs are being used so widely, with such ill effects, without being first tested or approved as safe and/or effective for pediatric use, always has something to say when the off label use of teratogenic drugs result in a child's death. He testified in a Senate hearing that he has NO IDEA why the drugs he himself recommends using off label and concomitantly in treatment guidelines and practice parameters, are being used in off label and concomitantly...
More importantly, what are the recommendations based on?
PRACTICE PARAMETER FOR THE ASSESSMENT AND TREATMENT OF
CHILDREN AND ADOLESCENTS WITH SCHIZOPHRENIA
PRACTICE PARAMETER FOR THE USE OF ATYPICAL ANTIPSYCHOTIC
MEDICATIONS IN CHILDREN AND ADOLESCENTS
This parameter was reviewed at the Member Forum at the AACAP Annual Meeting in
From January 2008 to October 2008 and from November 2010 to June 2011, this
parameter was reviewed by a Consensus Group convened by the CQI. Consensus Group
members and their constituent groups were as follows: CQI (Oscar Bukstein, M.D., chair and
shepherd; Allan Chrisman, M.D., John Hamilton, M.D., and Matthew Siegel, M.D., members);
Topic Experts (Jon McClellan, M.D. and Christopher McDougle, M.D.); AACAP Assembly of
Regional Organizations (Sherry Barron-Seabrook, M.D. and Gail Edelsohn, M.D.); and AACAP
Council (David R. DeMaso, M.D. and Melvin Oatis, M.D.).
This practice parameter was approved by the AACAP Council on August 2, 2011 here
Practice Parameter for the Assessment and Treatment of Children and Adolescents With Bipolar DisorderAccepted August 15, 2006.
This parameter was developed by Jon McClellan, M.D., Robert Kowatch, M.D.,
Robert L. Findling, M.D.,
This parameter was reviewed at the member forum in October 2004 at the
annual meeting of the American Academy of Child and Adolescent Psychiatry.
During August 2005, a consensus group reviewed and finalized the content of
this practice parameter. The consensus group consisted of representatives of relevant
AACAP components as well as independent experts: Oscar Bukstein, M.D., Work
Group Co-Chair; Jon McClellan, M.D., author here
Summary of the Practice Parameters for the Assessment and Treatment of Children and Adolescents with Depressive Disorders
Practice Parameter for the Use of Stimulant Medications in the Treatment of Children, Adolescents, and Adults
via Alliance for Human Research Protection
Evidence of Neuroleptic Drug-Induced Brain Damage in Patients:
Evidence of Neuroleptic Drug-Induced Brain Damage in Patients:
A partial, Annotated Bibliography
by Vera Hassner Sharav
For distribution: January, 2000
Although patients, families and the public were not informed - some would argue they were deceived - clinical psychiatrists and researchers have long known about severe adverse drug reactions (ADR) and disabling changes in the central nervous system in a high percentage of patients taking standard neuroleptic drugs. Foremost among these is "tardive dyskinesia" (TD), an often irreversible, disfiguring disorder of the central nervous system resulting in a variety of involuntary movements, particularly of the tongue, lips, and jaw. muscle movements which affects 40% to 60% of patients taking neuroleptics. Recent research findings corroborate earlier reports (since 1970) linking TD to a deterioration of cognitive functions (see below).
Other severe ADRs include: "extrapyramidal symptoms" (EPS), Parkinson-like, impaired motor coordination; sedation; extreme restlessness ("akathesia"); reduced cognitive function;as well as cardiovascular effects, orthostatic hypotension, abnormal liver changes, anticholinergic side effects, sexual dysfunction, and weight gain. Psychotic relapse has been linked to long-term neuroleptic treatment --referred to as, "supersensitivity psychosis." Additionally, there is a one percent risk of "neuroleptic malignant syndrome" (NMS), a potentially fatal side effect. These, and a host of other adverse side effects, cause most schizophrenia patients to stop taking these drugs.
In an article written in 1986, Tardive Dyskinesia: Barriers to the Professional Recognition of Iatrogenic Disease, [Journal of Health and Social Behavior,1986, 27: 116-132], Brown and Funk stated: "tardive dyskinesia (TD), once regarded by psychiatrists as a rare syndrome, is currently recognized as the second most pervasive side effect following sedation of antipsychotic drugs." Although evidence linking TD to neuroleptic drugs had been shown since 1957, Brown and Funk point out that the recognition of TD as a side effect had been "a slow and uneven process, involving psychiatric resistance....Even when physicians believe that patients should be informed about the risks of TD, usually only incomplete information is given, not all patients at risk are informed...." And, they noted, "psychiatrists who are critical of the profession's lax treatment of the problem argue that if doctors were really concerned, they would reduce their use of neuroleptics and reduce dosages when drugs are employed..." and they would fully disclose the risks of TD to their patients.
But a review of the history of TD demonstrates clearly that despite the evidence physicians' disclosure and practice with respect to neuroleptic drugs has remained unchanged, and TD afflicts ever more patients, especially after long-term exposure-estimates range between 40% to 60%. The APA has opposed written informed consent from patients.
Van Putten T, Marder SR (1987) Behavioral toxicity of antipsychotic drugs. J Clin Psychiatry 1987 Sep;48 Suppl:13-9
Extrapyramidal symptoms cause much misery, often go undiagnosed, and can interfere with treatment and rehabilitation. Akinesia is a behavioral state of diminished motoric and psychic spontaneity that is difficult to distinguish from the negative symptoms of schizophrenia. The most useful clinical correlates of akinesia are a subjective sense of sedation and excessive sleeping. Akinesia interferes with social adjustment and may manifest as "postpsychotic depression." The subjective restlessness of akathisia is usually accompanied by telltale foot movements: rocking from foot to foot while standing or walking on the spot. Akathisia is strongly associated with depression and dysphoric responses to neuroleptics and has even been linked to suicidal and homicidal behavior in extreme cases.
Recent Findings Corroborate high incidence of drug-induced movement disorders:
Miller LG, Jankovic J (1990) Neurologic approach to drug-induced movement disorders: a study of 125 patients.South Med J 1990 May;83(5):525-32. Department of Family Medicine, Baylor College of Medicine, Houston, Tex.
Of 125 patients with neuroleptic (dopamine blocking) drug-induced movement disorders who had been referred to a specialized clinic to differentiate the predominant movement disorder, 63% had tardive dyskinesia, 30% had parkinsonism, 24% had dystonia, 7% had akathisia, and 2% had isolated tremor. Two or more movement disorders coexisted in 31 patients (25%).
Functional disability was more severe in patients with akathisia than in other patients. Women outnumbered men at a ratio of 4:1, except for tardive dystonia which affected both sexes equally. The average at onset was 56 years (range, 13 to 87); 69 patients (55%) had onset of movement disorder in the sixth decade. While tardive dystonia was distributed relatively evenly in all age groups, almost a third of patients with parkinsonism had it in the eighth decade. Haloperidol was implicated in 47 patients (37%), followed by amitriptyline/perphenazine in 30%, thioridazine in 27%, and chlorpromazine in 20%. Metoclopramide-induced movement disorders were found in 10 (8%). Most patients (101 or 81%) had history of psychiatric illnesses, but of these only 44 had psychosis.
Neuroleptic drugs had been prescribed for 33 patients (26%) who had gastrointestinal problems. It is important to recognize and differentiate various drug-induced movement disorders because such differentiation has pathophysiologic and therapeutic implications. Many patients could have been treated with less potent drugs.
Muscettola G, Barbato G, Pampallona S, Casiello M, Bollini P (1999) Extrapyramidal syndromes in neuroleptic-treated patients: prevalence, risk factors, and association with tardive dyskinesia. J Clin Psychopharmacol 1999 Jun;19(3):203-8
ABSTRACT: Prevalence and risk factors for extrapyramidal syndromes (EPS) were investigated in a sample of 1,559 patients. The overall prevalence of EPS was 29.4% (N = 458). Among the EPS-diagnosed patients, Parkinsonism as assessed by the presence of core Parkinsonian symptoms (rigidity, tremor, bradykinesia) was present in 65.9% of patients (N = 302), akathisia in 31.8% (N = 145), and acute dystonia in 2.1% (N = 10).
EPS was diagnosed in 50.2% of 285 patients with persistent tardive dyskinesia (TD). Distribution of EPS in patients with TD showed that tremor and akathisia were more frequent in peripheral TD cases than in orofacial TD cases. Furthermore, there was a stronger association of NL-induced parkinsonism with peripheral TD than with orofacial TD. This study suggests that the association between EPS and TD may be limited to specific subtypes of TD. Peripheral TD showed a higher association with parkinsonism and with akathisia, suggesting that these symptoms may share a common pathophysiology.
Bristow MF, Hirsch SR (1993) Pitfalls and problems of the long term use of neuroleptic drugs in schizophrenia. Drug Safety 1993 Feb;8(2):136-48. Academic Department of Psychiatry, Charing Cross and Westminster Medical School, London, England.
ABSTRACT: Although acute and immediate extrapyramidal syndromes are common and, in the case of neuroleptic malignant syndrome, may have serious sequelae, the most important problem with psychotropic medication in schizophrenia remains the tardive movement disorders. These are increasingly recognised as being aetiologically as well as symptomatically heterogeneous. Although risk factors are being identified with greater clarity, there is little in the way of effective treatment. This suggests that clinicians must embark on long term neuroleptic treatment with vigilance. Clozapine alone has few extrapyramidal effects, and has been described in isolated instances as improving established movement disorders. However, haematological idiosyncrasies will preclude its use in all where compliance is uncertain. Its superior efficacy will hopefully give impetus to research into safer analogues.
Hansen TE, Brown WL, Weigel RM, Casey DE (1992) Underrecognition of tardive dyskinesia and drug-induced parkinsonism by psychiatric residents. Gen Hosp Psychiatry 1992 Sept; 14(5):340-4. Portland Veterans Affairs Medical Center, Oregon Health Sciences University 97207.
Recognition of tardive dyskinesia (TD) and other neuroleptic, drug-induced, extrapyramidal side effects presents a major challenge in modern clinical psychopharmacology. Failure to recognize these disorders can lead to poor patient care and may contribute to societal pressure for external control of psychiatric practice. This study reports the occurrence of tardive dyskinesia and drug-induced parkinsonism (DIP) in 101 inpatients, and documents under recognition of both disorders by resident physicians.
Researchers noted TD in 28% of cases and residents only described TD (or symptoms ofTD) in 12%. The researcher determined DIP prevalence rate of 26% contrasted with an 11% rate found by residents. Patients with psychotic disorders were more likely than other patients to have researcher-identified TD, whereas DIP (researcher cases) occurred more often in patients with affective diagnoses. Residents tended to miss milder cases of TD, and to miss DIP in younger patients and in patients with affective disorders. Improved teaching and clinical exams are recommended to improve recognition.
Neuroleptic drug induced psychotic relapse ("supersensitivity psychosis")
Chouinard G. Severe cases of neuroleptic-induced supersensitivity psychosis. Diagnostic criteria for the disorder and its treatment. Schizophr Res 1991 Jul-Aug;5(1):21-33 Psychiatric Research Center, Louis-H. Lafontaine Hospital, University of Montreal, Quebec, Canada.
ABSTRACT: Tardive dyskinesia is thought to result from neostriatal dopaminergic receptor supersensitivity induced by chronic treatment with neuroleptics. Similarly, receptor supersensitivity occurring in other dopaminergic regions of the brain could result in the development of supersensitivity psychosis. As with tardive dyskinesia, severe forms of the disorder are rare. Ten such cases are described whose main characteristic is that psychotic symptoms can no longer be masked by increased dosages of neuroleptics. Diagnostic criteria for the disorder are proposed, and treatment with antiepileptic medication is described.
Kirkpatrick B, Alphs L, Buchanan RW (1992) The concept of supersensitivity psychosis. J Nerv Ment Dis 1992 Apr;180(4):265-70. Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore 21228.
ABSTRACT: The hypothesis that chronic neuroleptic treatment may induce relapse in some schizophrenic patients has received considerable attention. This effect, usually called supersensitivity psychosis, has been attributed to neuroleptic-induced changes in mesolimbic or mesocortical dopaminergic receptors. However, research has not established that neuroleptics cause the proposed effect, and considerations of mechanism have not been separated from those of causation. The focus of research in this area should be the establishment or refutation of a causal relationship between chronic neuroleptic use and psychotic relapse.
Chouinard G, Sultan S. Treatment of supersensitivity psychosis withantiepileptic drugs: report of a series of 43 cases. Psychopharmacol Bull 1990;26(3):337-41. Allan Memorial Institute, Montreal, Quebec, Canada.
Supersensitivity psychosis has emerged as a potential side effect of long-term neuroleptic therapy that may be similar to tardive dyskinesia. Schizophrenic patients with supersensitivity psychosis and considered to be drug-resistant were treated with anti-epileptic medication. Forty-three separate trials were conducted on a total of 35 patients. Over half improved on clinical global impression, some of them considerably. We propose that antiepileptic drugs ameliorate supersensitivity psychosis and so-called "drug-resistant" schizophrenic patients by correcting a pharmacological kindling effect in the limbic system which results from chronic neuroleptic therapy. Publication Types: Clinical trial
Kahne GJ. Rebound psychoses following the discontinuation of a high potency neuroleptic. Can J Psychiatry 1989 Apr;34(3):227-9
Increased familiarity with the effects of psychotropic medications has led to modifications in both prescribing habits and length of treatment. The case of a 34 year old woman is presented, in whom the return of psychotic symptoms following the discontinuation of neuroleptic medications is attributed to a rebound phenomena as opposed to a relapse of an underlying chronic illness
The author cites parallel situations previously described in the medical literature and outlines a conceptual framework for the understanding of this phenomenon.
Bowers MB Jr, Swigar ME. Psychotic patients who become worse on neuroleptics. J Clin Psychopharmacol 1988 Dec;8(6):417-21. Yale University School of Medicine, Department of Psychiatry, New Haven, Connecticut
ABSTRACT: We describe a group of psychotic patients who became worse early in the course of neuroleptic treatment. Characteristics of this group were: predominantly female sex, relatively brief onset, family history of affective disorder, hypomotoric presentation, and severe neuroleptic side effects. We propose that some patients with affective psychoses are uniquely susceptible to profound blockade of the nigrostriatal dopaminergic system by neuroleptics.
During the 1990s, the "Decade of the Brain:"
Newer "atypical" neuroleptics have been developed-clozapine, risperdone, olanzapine and quitepane-these drugs have a lower risk of EPS and TD, but are associated in varying degrees with sedation, cardiovascular and liver enzyme abnormalities, anticholinergic effects, extreme weight gain (30lbs to 50lbs) which significantly increases the risk for diabetes, sexual dysfunction, NMS, seizures, mania, and (in the case of clozapine) agranulocytosis.
Additionally, mounting clinical evidence and findings -from non-industry sponsored research-point to additional, severe, adverse neurological changes in response to long-term exposure to neuroleptics. These drugs' actions suppress certain brain receptors (e.g., dopamine, glutamate), and when such drugs are withdrawn (or a patient stops taking them) the drug-induced receptor changes are unmasked, causing an acute "discontinuation syndrome" (i.e., "rebound psychosis" ) that is often more severe than the original symptoms of the illness. Psychotic relapse can cause months of mental and emotional anguish and loss of functioning-rebound psychosis can cause violent and suicidal behavior in patients not previously violent. [Often, these drug-induced reactions are used to justify forcing the person back on the drugs.]
Collaborative Working Group on Clinical Trial Evaluations. Adverse effects of the atypical antipsychotics. J Clin Psychiatry 1998; 59 Suppl 12:17-22
ABSTRACT: Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain.
The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.
Wyderski RJ, Starrett WG, Abou-Saif A. Fatal status epilepticus associated with olanzapine therapy. Ann Pharmacother 1999 Jul-Aug;33(7-8):787-9. Department of Internal Medicine, School of Medicine, Wright State University, Dayton, OH 45409, USA. email@example.com
OBJECTIVE: To report a case of fatal status epilepticus in a patient using olanzapine with no known underlying cause or predisposing factor for seizure. CASE SUMMARY: A 41-year-old white woman developed witnessed seizures at home that progressed to status epilepticus. She subsequently died from secondary rhabdomyolysis and disseminated intravascular coagulation.She had been taking olanzapine for five months prior to the event. No other toxic, metabolic, or anatomic abnormalities were identified pre- or postmortem to explain the seizures. Her seizures were a probable adverse drug reaction based on the Naranjo scale.
DISCUSSION: This is the first case of fatal status epilepticus described that has been associated with the use of olanzapine. The pharmacodynamics of olanzapine are similar to those of clozapine, which has been described to induce seizures in 1-4% of patients. It is possible that this patient may have suffered seizures due to a similar effect. Alternate explanations include neuroleptic malignant syndrome and alcohol or benzodiazepine withdrawal seizures, although her clinical history does not suggest these etiologies.
CONCLUSIONS: Although olanzapine has infrequently been associated with seizures in premarketing studies, its potential to induce them exists. Postmarketing surveillance should continue to determine how significant this effect may be.
Drug induced "rebound psychosis" & Mania
Shore D. Clinical implications of clozapine discontinuation: report of an NIMH workshop. Schizophr Bull 1995;21(2):333-8. Division of Clinical and Treatment Research, NIMH, Rockville, MD 20857, USA.
ABSTRACT: In September 1994, the National Institute of Mental Health convened a group of scientists to discuss the clinical effects of rapid clozapine discontinuation, especially in light of the introduction of risperidone for the treatment of schizophrenia. Despite concern over recent reports of clinical deterioration (psychotic exacerbations, somatic withdrawal symptoms, and extrapyramidal side effects) in a few patients abruptly discontinued from clozapine, there is currently insufficient information to determine the magnitude of the problems associated with clozapine withdrawal.
However, clinicians are reminded that the withdrawal schedule for clozapine indicates a gradual tapering schedule (unless the patient is experiencing severe side effects); that switching patients from clozapine to risperidone does not mean that such tapering is unnecessary; and that the use of risperidone may not produce all of the same effects as clozapine in some treatment-refractory patients. PMID: 7543218, UI: 95357664
Stanilla JK, de Leon J, Simpson GM. Clozapine withdrawal resulting in delirium with psychosis: a report of three cases. J Clin Psychiatry 1997 Jun;58(6):252-5. Department of Psychiatry, Allegheny University, Norristown State Hospital, Pa. 19401, USA.
BACKGROUND: Withdrawal symptoms for typical antipsychotics are generally mild, self-limited and do not include development of psychotic symptoms. In contrast, withdrawal symptoms for clozapine can be severe with rapid onset of agitation, abnormal movements, and psychotic symptoms. Different pathophysiologic etiologies have been suggested for these severe symptoms, including dopaminergic supersensitivity and rebound. METHOD: Three case reports of clozapine withdrawal symptoms are presented. A review of previous case reports and discussion of the etiology of withdrawal symptoms of typical antipsychotics and clozapine are provided.
RESULTS: These three patients developed delirium with psychotic symptoms that resolved rapidly and completely upon resumption of low doses of clozapine.
CONCLUSION: The severe agitation and psychotic symptoms after clozapine withdrawal in these three patients were due to delirium, perhaps the result of central cholinergic rebound. The withdrawal symptoms and delirium resolved rapidly with resumption of low doses of clozapine. Severe withdrawal symptoms can probably be avoided by slowly tapering clozapine and/or simultaneously substituting another psychotropic with high anticholinergic activity, such as thioridazine.
Durst R, Teitelbaum A, Katz G, Knobler HY (1999) Withdrawal from clozapine: the "rebound phenomenon". Isr J Psychiatry Relat Sci 1999;36(2):122-8. Jerusalem Mental Health Center, Kfar Shaul Hospital, Israel.
Clozapine is an "atypical" antipsychotic agent for treating previously resistant schizophrenic patients. Its main advantages over "typical" neuroleptics are low incidence of extrapyramidal side effects and its capacity to induce therapeutic response in previously treated refractory patients. However, withdrawal from clozapine has been observed to lead to "atypical" clinical characteristics or a "rebound phenomenon," manifested in two interwoven clinical forms: (1) psychotic exacerbation, and (2) cholinergic rebound. The underlying pathophysiological mechanism of this phenomenon is postulated to be a result of cholinergic supersensitivity. In this paper, the "rebound phenomenon" will be discussed and exemplified by three case histories in which abrupt cessation of clozapine led to serious deterioration and psychotic exacerbation, and one case in which gradual titration from the drug was employed in order to preempt this hazardous occurrence. PMID: 10472746, UI: 99401971
Still DJ, Dorson PG, Crismon ML, Pousson C Effects of switching inpatients with treatment-resistant schizophrenia from clozapine to risperidone. Psychiatr Serv 1996 Dec;47(12):1382-4. Department of Psychiatry, Community Hospitals Indianapolis, IN 46219, USA.
A prospective, open-label study in a 400-bed state psychiatric hospital evaluated change in therapeutic response among ten patients with treatment-resistant schizophrenia who were switched from clozapine to risperidone. Drug effects were examined before discontinuation of clozapine and at three, six, nine, and 12 weeks of risperidone treatment. No patients improved, and five discontinued treatment due to exacerbation of psychosis or adverse effects. Changes in scores on the Positive and Negative Syndrome Scale, the Brief Psychiatric Rating Scale, and the Barnes Akathisia Scale indicated clinically significant worsening of symptoms. The findings do not support replacing clozapine with risperidone for patients with treatment-resistant schizophrenia.
Delassus-Guenault N, Jegouzo A, Odou P, Seguret T, Zangerlin H, Vignole E, Robert H. Clozapine-olanzapine: a potentially dangerous switch. A report of two cases. J Clin Pharm Ther 1999 Jun;24(3):191-5. Department of Pharmacy, EPSM Lille-Metropole, Armentieres, France.
BACKGROUND: Withdrawal symptoms associated with switch between two typical antipsychotics are generally rare and mild. In contrast, switching from clozapine to risperidone can be lead to severe withdrawal symptoms. Different pathophysiologic aetiologies have been suggested for explaining these severe symptoms, including cholinergic supersensitivity and rebound. Theoretically, the switch from clozapine to olanzapine should not lead to any problems because those two agents have the same affinity in vitro for muscarinic receptors. OBJECTIVE: This study reports two cases of switches from clozapine to olanzapine, in refractory schizophrenic patients, which were associated with severe withdrawal symptoms.
RESULTS: After the switch, the two patients developed diaphoresis, hypersialorrhea, bronchial obstruction, agitation, anxiety and enuresis. The symptoms were treated with anticholinergic medication and by an increase in dose of olanzapine to 20 mg/day. For one of the patients this treatment led to normalization of secretion. For the other patient, a superinfection leading to a bilateral pneumopathy which required emergency hospitalization in a general hospital was observed.
CONCLUSION: The symptomatology and the response to treatment lead to the hypothesis of a muscarinic from abrupt weaning. The withdrawal symptoms disappeared rapidly with an increase in olanzapine dosage and with anticholinergic started at the beginning of the switch. We recommend slow clozapine weaning over 3 weeks or more with concurrent anticholinergic treatment.
Ekblom B, Eriksson K, Lindstrom LH. Supersensitivity psychosis in schizophrenic patients after sudden clozapine withdrawal. Psychopharmacology (Berl) 1984;83(3):293-4.
In two patients with chronic schizophrenia, who were on clozapine medication for more than 6 months, a sudden withdrawal of the drug resulted in a very pronounced deterioration of the psychosis within 24-48 h. The most prominent symptoms were auditory hallucinations and persecutory ideas and one patient tried to commit suicide. These observations are interpreted as supersensitivity psychoses induced by the very effective clozapine treatment.
Jauss M, Schroder J, Pantel J, Bachmann S, Gerdsen I, Mundt C. Severe akathisia during olanzapine treatment of acute schizophrenia. Pharmacopsychiatry 1998 Jul;31(4):146-8. Department of Psychiatry, University of Heidelberg, Germany. Jauss@USA.net
Olanzapine is a newly developed atypical neuroleptic with a marked affinity to the 5-HT2, D2 and D4 dopamine receptors. Like other atypical neuroleptics olanzapine is considered to show a reduced prevalence of extrapyramidal side effects when compared to classical neuroleptic drugs.
We report on three patients with acute schizophrenia, who developed severe akathisia during treatment with olanzapine (20-25 mg/d). In two of these cases akathisia resolved after withdrawal of olanzapine and substitution by a classical or an atypical neuroleptic agent, respectively. In one of these patients olanzapine was well tolerated when reintroduced in combination with lorazepam after complete remission of akathisia.
In the third patient akathisia as sufficiently controlled by dose reduction. Akathisia is generally considered to result from D2 dopamine receptor antagonism. In the case of atypical neuroleptics such as olanzapine a low but still considerable D2 dopamine receptor occupancy may be compensated by the 5-HT2 antagonism. However, this mechanism may fail under certain circumstances, in particular if D2 dopamine antagonism exceeds a certain threshold. One should therefore be aware of possible extrapyramidal side effects with olanzapine that are reduced compared to classical neuroleptic drugs but not completely eliminated.
Molho ES, Factor SA (1999). Worsening of motor features of parkinsonism with olanzapine. Mov Disord 1999 Nov;14(6):1014-6. Department of Neurology, Albany Medical College, New York, USA.
Clozapine is the current treatment of choice for drug-induced psychosis (DIP) occurring in Parkinson's disease. However, alternative medications have been sought because of the small but significant risk of agranulocytosis and the need for frequent blood testing. The new "atypical" antipsychotic olanzapine (OLZ) has recently been proposed as a safe and effective option for treating psychosis in this setting. To investigate this, we retrospectively evaluated all 12 of our patients treated with OLZ for DIP. Symptoms of psychosis were improved in nine of 12 patients, but nine of 12 patients also experienced worsening of motor functioning while on OLZ. The worsening was considered dramatic in six of these patients. Overall, there was no significant increase in levodopa doses on OLZ. Only one patient remained on OLZ at the time of the analysis. Nine patients were switched to alternative treatment for DIP.
"We conclude that although Olanzapine may improve symptoms of psychosis in parkinsonian patients, it can also worsen motor functioning. In some patients, the degree of motor worsening may be intolerable." read the rest here