Antipsychotics for schizophrenia

A little girl of 1 7 in a mental hospital told me she was terrified because the atom bomb was inside her. That is a delusion. The statesmen of the world who boast and threaten that they have Doomsday weapons are far more dangerous and far more estranged from reality than many of the people on whom the label psychotic is fixed. 

The core problem with the antipsychiatry approach is its practical limitations. How exactly does it assist the distressed individual who is suffering from the delusion that they have an atomic bomb inside their body It will be shown later that psychotherapy without drug treatment is largely ineffective (as Jung and Fried both concluded), whereas psychological therapy combined with active drug treatment is the most effective therapeutic approach. 

The following case study illustrates many of the core aspects of this devastating disorder  

You may have noticed a number of features of the disorder in this case study. However, it is important to note that not all people with schizophrenia show these very symptoms and that there are other symptoms not evident here. However, the case illustrates several archetypal aspects of schizophrenia. First, it is a young person s disease. Second, it has a similar frequency of occurrence in both sexes, unlike many psychiatric 

Disorganised thought Thought insertion, blocking and retrieval neologisms or the 

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Mahmoud RA, Engelhart LM, Janagap CC, Oster G, Ollendorf D. Risperidone versus conventional antipsychotics for schizophrenia and schizoaffective disorder. Symptoms, quality of life and resource use under customary clinical care. Clin Drug Invest 2004 24 275-86. 

As noted earlier, when a primary psychiatric disorder is diagnosed, generally medication treatment targets the primary illness, such as antipsychotics for schizophrenia or antidepressants for agitated depression. 

Komossa K, Rummel-Kluge C, Schmid F, Hunger H, Schwarz S, El-Sayeh HG, Kissling W, Leucht S. Aripiprazole versus other atypical antipsychotics for schizophrenia. Cochrane Database Syst Rev 2009 (4) CD006569. 

Psychopharmaco-epidemiology investigation in China in 2002 showed that the first six antipsychotic drugs used for schizophrenia were clozapine, risperidone,... 

Chong, M. Y., Tan, C. H., Fujii, S. et al. (2004). Antipsychotic drug prescription for schizophrenia in East Asia rationale for change. Psychiatry Clin. Neuroscl, 58(1), 61-7. 

Reserpine inhibits the synaptic vesicular storage of the monoamines dopamine, serotonin and noradrenaline. As a result they leak out into the cytoplasm where they are inactivated by monoamine oxidase this causes their long-lasting depletion. The resulting low levels of dopamine underlie the antipsychotic actions of reserpine (Chapter 11), whereas the reduced noradrenaline levels underlie its antihypertensive actions. Finally, the resulting low levels of serotonin and noradrenaline mean that reserpine also induces depression. These severe side effects mean that reserpine is no longer used clinically as a treatment for schizophrenia (Chapter 11). 

The positive symptoms are the most responsive to antipsychotic medications, such as chlorpromazine or halo-peridol. Initially, these drugs were thought to be specific for schizophrenia. However, psychosis is not unique to schizophrenia, and frequently occurs in bipolar disorder and in severe major depressive disorder in which paranoid delusions and auditory hallucinations are not uncommon (see Ch. 55). Furthermore, in spite of early hopes based on the efficacy of antipsychotic drugs in treating the positive symptoms, few patients are restored to their previous level of function with the typical antipsychotic medications [2]. 

FIGURE 58-7 The IC50 values (ordinate) are the concentrations of the antipsychotic drugs that reduce the stereospecific component of 3H-haloperidol binding by 50%. The abscissa indicates the average values (and ranges) of doses used for schizophrenia. (From Seeman, P. et al. Antipsychotic drug doses and neuroleptic/dopamine receptors. Nature 261 717-719,1976)... 

Whatever the underlying causes may be, neuroleptic medications are the most effective treatment for schizophrenia. All antipsychotic medications have some form of dopamine receptor antagonism and they are distinguished by their chemical class. The phenothiazines include chlorpromazine (Thorazine), thioridazine (Mellaril), mesoridazine (Serentil), trifluoperazine (Stelazine), fluphenazine (Prolixin), and prochlorperazine (Compazine). The thioxanthenes include chlorprohixine (Taractan) and thiothixene (Navane). Butyrophenones are represented by haloperidol (Haldol). Loxapine (Loxitane) is a dibenzoxapine, and molindone (Moban) is a dihydroindolone. 

The first of the second-generation, or atypical, antipsychotics was clozapine. Clozapine (Clozaril) is relatively free of the movement disorders that characterize the first-generation drugs. This is true of, and defines, second-generation, atypical antipsychotics. It was a significant breakthrough for schizophrenia patients. 

Lithium (Eskaiith, Lithobid). Before the recent proliferation of atypical antipsychotics, lithium was tried as an alternative for schizophrenia. By and large, this represented another effort to circumvent the risk of tardive dyskinesia. It is not effective either as monotherapy or as combination therapy with antipsychotics in schizophrenia. 

The second revolution began in the past 10 years with the arrival of the atypical antipsychotics. Although the atypicals are no panacea for schizophrenia, they represent an advance in at least three areas. First, they lessen the burden of antipsychotic side effects and therefore frequently increase adherence dramatically. Second, the atypicals may treat all of the schizophrenia symptom clusters (positive, negative, mood, cognitive), whereas the typical antipsychotics chiefly treat the positive symptoms. Third, atypical antipsychotics sometimes benefit patients whose schizophrenia is unresponsive to typical antipsychotics. 

Kelleher JP, Centorrino F, Albert Ml, et al. Advances in atypical antipsychotics for the treatment of schizophrenia new formulations and new agents. CNS Drugs 2002 16(4) 249-261. 

Schizophrenia - When deciding among the alternative treatments available for schizophrenia, consider ziprasidone s greater capacity to prolong the QT/QTc interval compared with other antipsychotic drugs. 

Hunter RH, Joy CB, Kennedy E, Gilbody SM, Song F. Risperidone versus typical antipsychotic medication for schizophrenia. Cochrane Database Syst Rev 2003. Issue 2. 

Tuunainen A, Wahlbeck A, Gilbody SM. Newer atypical antipsychotic medication versus clozapine for schizophrenia. Cochrane Database of Systematic Reviews 2000. Issue 2. 

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