National Center for Mental Health

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1 National Center for Mental Health 9 de Febrero St., Mandaluyong City Telephone No.: Organizational Structure Medical Center Chief II Chief, Medical and Professional Staff (Hospital Service) Chief, Medical and Professional Staff (Community Service) Treatment Protocol Committee (Schizophrenia) Bernardino A. Vicente, M.D., FPPA, MHA, CESO IV Rosalinda E. Castañeda, M.D., FPPA Venus S. Arain, M.D., FPPA, MHA Emely G. Jardiolin, M.D., DPBP Noel V. Reyes, M.D., DPBP Victor C. Vinluan, Jr., M.D., FPPA, MHA

2 Guidelines in the Treatment of Schizophrenia I. Definition A clinical syndrome that manifests with multiple signs and symptoms involving thought, perception, emotion, movement, and behavior. The manifestations combine in various ways, creating considerable diversity among patients, but the cumulative effect of the illness can be severe and long lasting. It affects 1 person in 1. II. Epidemiology Lifetime Prevalence: cases per 1, population Sex: Equally prevalent in men and women Age: Men - between 15 and 25 years of age Women - between 25 and 35 years of age About 9% of the patients in treatment for schizophrenia are between 15 and 55 years old Birth and Fetal Complications: Schizophrenic persons as a group experience a greater number of birth complications, especially male infants. Studies have also reported a relationship between perinatal complications and early onset of disease, negative symptoms, and poorer prognosis. The reason for the increased risk is unknown but the following plausible explanations guide present day research. 1. The genes that create vulnerability for schizophrenia may also alter early embryonic development in a manner that increases the likelihood of gestational and birth complications. 2. Hypoxia: components of the limbic system, the cerebral cortex and the basal ganglia brain regions most frequently implicated, as deviant in schizophrenia are among the areas in the developing brain most susceptible to the adverse effects of hypoxia. Social Class: Studies report a higher prevalence rate among members of lower social class than upper social class. This would imply that socioeconomic factors found at lower socioeconomic levels are a cause of schizophrenia. Another implication is that a low socioeconomic status is a consequence of the disorder. III. Etiology A. Major Biochemical Theories The evidence for the role of dopamine, especially dopamine excess remains a viable explanation for the development of the symptoms of schizophrenia. Recent reports have implicated serotonin hyperactivity as well in relation to the suicidal and impulsive behavior seen in schizophrenic patients. Other neurotransmitters such as norepinephrine and GABA have been implicated but are still inconclusive. B. Major Neuroanatomical Theories Delineation of the mesolimbic and mesocortical dopaminergic pathways in the brain led to the hypotheses postulating the involvement of the limbic system, the frontal cortex, or both on the pathophysiology of schizophrenia. Also implicated are the basal ganglia - thalamocortical neural circuits. C. Genetic Hypotheses Schizophrenia manifestations occur at an increased rate among the biological relatives of patients with schizophrenia and that the likelihood of the person's having schizophrenia is correlated with the closeness of the relationship. Prevalence of schizophrenia in specific populations: (See Table 1.) D. Psychodynamic Theory Presence of an ego defect affects the interpretation of reality and the control of inner drives, such as sex and aggression. The disturbances occur as a consequence of distortions in the reciprocal relationship between the infant and the other. Object constancy described as a sense of security which results from a close attachment to the mother during infancy is not achieved. Table 1. Population Prevalence (%) Non-twin sibling of a schizophrenic patient Child with one schizophrenic parent Dizygotic twin of a schizophrenic patient Child of 2 schizophrenic patients Monozygotic twin of a schizophrenic patient

3 IV. Symptomatology Symptoms of schizophrenia may be divided into two basic categories namely, the positive symptoms and the negative symptoms. A. Positive Symptoms 1. Hallucinations - false sensory perception not associated with real external stimuli. Auditory hallucinations are the most common, although tactile, visual, and olfactory hallucinations may also occur. 2. Delusions - false belief based on incorrect inference about external reality, not consistent with patient's intelligence and cultural background and that which cannot be corrected by reasoning. May be persecutory, jealous, grandiose, religious or somatic in nature. 3. Disorganized behavior - odd/bizarre behaviour and appearance; aggressive/agitated behavior; repetitive/stereo-typed behavior 4. Disorganized Speech - incoherent and illogical speech B. Negative Symptoms 1. Affective flattening: unchanging facial expression decreased spontaneous movement poor eye contact inappropriate affect lack of vocal inflections 2. Alogia: poverty of speech blocking increased response latency 3. Avolition - Apathy: poor grooming and hygiene impersistence at work or school physical anergia 4. Anhedonia - Asociality: lack of involvement in recreational interests poor interpersonal relationships with peers and family members 5. Attention: Social inattentiveness Diagnostic Criteria for Schizophrenia: CPM 6 TH edition A. Two or more of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated) 1. delusions 2. hallucinations 3. disorganized speech 4. grossly disorganized or catatonic behavior 5. negative symptoms B. Social/occupational dysfunction: one or more major areas of functioning such as work, interpersonal relations, or self-care, are markedly below the level achieved prior to the onset. C. Continuous signs of the disturbance persist for at least six months. This six month period must include at least 1 month of symptoms that meet criterion A and may include periods of prodromal or residual symptoms. During these prodromal or residual periods, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in criterion A present in an attenuated form. D. Schizoaffective disorder and mood disorder with psychotic features have been ruled out because either: (1) no major depressive, manic, or mixed episodes have occurred concurrently with the active-phase symptoms; or (2) if mood episodes have occurred during the active phase symptoms, their total duration has been brief relative to the duration of the active and residual symptoms. E. The disturbance is not due to the direct physiological effects of a substance or a general medical condition. F. If there is a history of autistic disorder or a pervasive developmental disorder, the additional diagnosis of schizophrenia is made only if prominent delusions or hallucinations, are also present for at least one month. The most common course is one of acute exacerbations and remissions, with increasing residual dysfunction between episodes. The course is however not uniform for every patient nor is progressive deterioration inevitable. Some patients recover completely, or some improve or recover even after a long period of illness. However, patients usually relapse and a further deterioration in the patient's baseline functioning follows each relapse of the psychosis. V. Treatment A. Consultation B. Hospitalization The acute or active phase is when symptoms of psycho-

4 sis such as delusions, hallucinations, and odd behavior are most prominent. It is at this phase that individuals are most likely to be brought to the attention of mental health workers. This will always require medical assessment. The need for assessment will be particularly urgent if the individual is at high risk of self harm or harm to others. Psychotic individuals who pose a substantial risk of danger to themselves or others may need hospital care. Aside from suicidal or homicidal behavior, other indications for hospitalization include grossly disorganized or inappropriate behavior, inability to take care of basic needs such as food, clothing, and shelter and for stabilization of medications. C. Pharmacotherapy Antipsychotic Medications : treatment with drugs is most often a cornerstone. The drugs used are called antipsychotics or neuroleptics. There are a number of drugs available for treatment and they may be roughly categorized into two groups: conventional and atypical. 1. Conventional antipsychotic drugs: These have been in use since many decades. They include drugs such as haloperidol, perphenazine, chlorpromazine, thioridazine, and trifluoperazine. They are effective primarily against positive symptoms of schizophrenia such as hallucinations and delusions. (See Table 2). At high doses, side effects are common. These include the so-called extrapyramidal symptoms such as tremor, muscle stiffness and unintended movements, as well as an experience of unrest and inability to be still. Often a low dose where no side effects are seen is sufficient for good effect. (See Table 3.) 2. Atypical antipsychotics: most of these drugs Table 2. Recommended Doses: Conventional Antipsychotics 1.Haloperidol 2. C h l o r p r o - mazine 3.Thioridazine have appeared in the later years. This group include risperidone, clozapine, olanzapine, and quetiapine. (See Table 4.) The drugs in this group share the good preventing effect against psychosis with the conventional drugs, but the risk of developing extrapyramidal effects is probably smaller. There is also scientific evidence pointing to a profitable effect of these drugs on negative symptoms and improved cognitive function. (See Table 5.) Rapid Tranquilization: Involves rapidly administering multiple doses of antipsychotic medication to achieve a decrease in acute psychotic symptoms. Used to treat violent, assaultive, or extremely agitated patients. Patients who have been tranquilized must have vital signs closely monitored. Medications used: Acute Dose Maintenance Dose For rapid sedation. Haloperidol 5 mg/ml given 1 ml intramuscularly given every hour. Three doses are usually sufficient to control the symptoms. 2. Atypical oral antipsychotics. Consider using atypicals for acute management if patient is able and willing to take oral medications. For example, risperidone 1-2 mg PO q 4-6 hours, Table 3. Adverse Effect Profile: Conventional Antipsychotics Sedation Hypotensive Anticholinergic Extrapyramidal effect effect symptoms Haloperidol Low Low Low High Chlorpromazine High High Medium Low Thioridazine High High High Low Trifluoperazine Medium Low Low High Levomepromazine High High Medium Low

5 CPM 6 TH edition Table 5. Adverse Effect Profile: Atypical Antipsychotics Clozapine Risperidone Olanzapine Quetiapine Amisulpride Ziprasidone Agitation Agranulocytosis Anticholinergic /- /- /- AST/ALT ele-vation Cardiac /- /- /- EPS Orthostatic hypotension /- Sedation /- /- Seizure Weight Gain /- Table 4. Recommended Doses: Atypical Antipsychotics 1.Risperidone 2.Olanzapine 3.Clozapine 4.Amisulpride 5. Quetiapine 6. Ziprasidone Acute Dose Maintenance Dose up to 8 mg /day, or olanzapine 5-1 mg PO q 4-8 hours up to 3 mg/day. These agents have fewer adverse effects especially with long term use. 3. Ziprasidone 2 mg/ml. Administer 1-2 mg up to a maximum dose of 4 mg/day. 1 mg may be administered every 2 hours while 2mg may be administered every 4 hours. Long acting depot medications: Because of poor compliance with oral medications in patients, long acting depot preparations are needed. They are usually given every 1 to 4 and may be associated with increased side effects. The preparation is injected into an area of large mus- cle tissue (buttocks or deltoid) from which they are absorbed slowly in the blood. 1. Fluphenazine decanoate 25 mg/ml, every Flupentixol decanoate 2 mg/ml, every Haloperidol decanoate 5 mg/ml, every 4 4. Pipothiazine palmitate, 25 mg/ml, every 4 5. Risperdal Consta 25 mg/ml, every 2-3 Maintenance Treatment: The first to three months after the psychotic episode is a period of stabilization for the patient. If a patient has improved with a particular drug regimen, he or she should continue taking the same medication at the same dose for the next 6 months before a lower maintenance dose is considered for continued treatment. Premature lowering of the dose or discontinuation of the medication during this phase may lead to a relatively rapid relapse. The dose may be decreased about 2% every six months until the minimum effective dose is found. After a first psychotic episode, medications may be discontinued after 2 years of maintenance medications. After a second episode, medications are maintained for 5 years. After the third psychotic episode, lifetime maintenance is recommended with attempts to reduce the dose every 6 to 12 months.

6 References: 1. Bernstein, J: Handbook of Drug Therapy in Psychiatry, 3 rd edition. Mosley- Year Book Inc., Missouri, Cassem, N.: Massachusetts General Handbook of General Psychiatry. Mosley Year Book Inc., St. Louis MO, Dunner, D.: Current Psychiatric Therapy III. WB Saunders Company, Pennsylvania, First,M., Frances A., et. al.: DSM IV Handbook of Differential Diagnosis. American Psychiatric Press, Hales, R., Yudofsky, S., et. al.: Text book of Psychiatry, 3 rd edition. The American Press, Hirsch, S., Weinberger, D.: Schizophrenia. Blackwell Science Ltd., London, Kaplan, H., Sadock, B.: Comprehensive Textbook of Psychiatry. 6 th edition. Williams & Wilkins, Baltimore, Kaplan, H., Sadock, B.: Pocket Handbook of Emergency Psychiatric Medicine. Williams & Wilkins, Baltimore, Kaplan H., Sadock, B.: Synopsis of Psychiatry, 8 th edition. Williams & Wilkins, Baltimore, Nemeroff, C., Schatzberg, A.: Recognition and Treatment of Psychiatric Disorders: A Psycho-pharmacology Handbook for Primary Care. American Psychiatric Press Inc., Washington D.C., Niesink, De Vries, Hollinger: Toxicology, Principles and Application, CRC Press Inc. and Open University of Netherlands, Bazire, Stephen, Psychotropic Drug Directory. Mark Allen Publishing Ltd., Jesses Farm Snow Hill, Dinton NR Salisbury, Wilts, Management of Mental Disorders, Volume 2, 2nd edition, World Health Organization Collaborating Centre for Mental Health and Substance Abuse, Articles 1. Antipsychotics- Drugs Against Schizophrenia by Pentus Stralin, MD, PhD Human Brain Informatics, American Psychiatric Association - Clinical Resources.

7 Drugs Mentioned in the Treatment Guideline This index lists drugs/drug classifications mentioned in the treatment guideline. Prescribing information of these drugs can be found in PPD reference systems. Antipsychotics Amisulpride Solian Chlorpromazine Laractyl Thorazine Psynor Clozapine Leponex Flupentixol decanoate Fluanxol Depot Flupentixol dihcl Fluanxol Fluphenazine decanoate Faulding/DBL Fluphenazine Decanoate Inj Modecate Phlufdek Haloperidol Faulding/DBL Haloperidol Decanoate Haldol Serenace Levomepromazine Nozinan Olanzapine Zyprexa Perphenazine Trilafon Quetiapine Seroquel Risperidone Risperdal Sulpiride Dogmatil Thioridazine Melleril Ziprasidone Zeldox Zuclopenthixol Clopixol

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