Depression positive symptoms

The tricyclic antidepressants (TCAs) derive their name from their three-ringed molecular structure (Fig. 20.3) and emerged, in 1958, from a search for better neuroleptics than chlopromazine among the phenothiazines. The prototype, imipramine, turned out to be ineffective in treating the positive symptoms experienced by schizophrenics but it did relieve their depression (negative symptoms). In fact, imipramine is still the standard agent against which novel antidepressants are compared in clinical trials. 

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]. 

The typical antipsychotic drugs, which for 50 years have been the mainstay of treatment of schizophrenia, as well as of psychosis that occurs secondary to bipolar disorder and major depressive disorder, affect primarily the positive symptoms[10]. The behavioral symptoms, such as agitation or profound withdrawal, that accompany psychosis, respond to the antipsychotic drugs within a period of hours to days after the initiation of treatment. The cognitive aspects of psychosis, such as the delusions and hallucinations, however, tend to resolve more slowly. In fact, for many patients the hallucinations and delusions may persist but lose their emotional salience and intrusiveness. The positive symptoms tend to wax and wane over time, are exacerbated by stress, and generally become less prominent as the patient becomes older. 

Misdiagnosis arises when undue emphasis is placed on symptoms such as ideas of reference Positive symptoms may occur and the onset is often rapid with relatively good premorbid functioning Distinctions such as mood congruency can be difficult to apply Negative symptoms may occur in depression... 

Investigators have attempted to assess the impact of antipsychotics on the cognitive and the behavioral disturbances characteristic of schizophrenia. The antipsychotics decrease typical, but nonspecific, positive symptoms such as hallucinations and delusions ( Table 5-4). Thus, labeling them as antischizophrenic agents is too restrictive inasmuch as they also benefit such disparate disorders as psychotic depression or mania, iate-onset paraphrenia, and organic-induced psychosis. As the symptoms reduced by neuroleptics are typical of psychosis in general, these agents are best conceptualized as a type of antipsychotic. 

Conley et al. (121) reported a large, double-blind study comparing risperidone with olanzapine. This study included about 400 patients randomly assigned to a flexible dose of risperidone (2 to 6 mg) or olanzapine (5 to 20 mg) for 8 weeks. On many measures, clinical improvement was the same however, risperidone did produce a slightly greater improvement than olanzapine on positive symptoms and on the anxiety/depression subscale. Most patients on risperidone received 4 to 6 mg/day, whereas half the patients on olanzapine received 10 mg and 10% received 5 mg. The mean dose of risperidone was 4.8 mg/day and for olanzapine 14.3 mg/day. 

Chlorpromazine Blockade of D2 receptors >> 5 2 receptors .-Receptor blockade (fluphenazine least) muscarinic (M)-receptor blockade (especially chlorpromazine and thioridazine) Hx-receptor blockade (chlorpromazine, thiothixene) t central nervous system (CNS) depression (sedation) t decreased seizure threshold t QT prolongation (thioridazine) Psychiatric schizophrenia (alleviate positive symptoms), bipolar disorder (manic phase) nonpsychiatric antiemesis, preoperative sedation (promethazine) pruritus Oral and parenteral forms, long half-lives with metabolism-dependent elimination Toxicity Extensions of effects on a - and M- receptors blockade of dopamine receptors may result in akathisia, dystonia, parkinsonian symptoms, tardivedyskinesia, and hyperprolactinemia... 

Disorders in addition to schizophrenia that can have positive symptoms include bipolar disorder, schizoaffective disorder, psychotic depression, Alzheimer s disease... 

FIGURE 10—3. Negative symptoms in schizophrenia can either be a primary deficit of the illness (1° deficit) or secondary to depression (2° to dep), secondary to extrapyramidal symptoms (2° to EPS), secondary to environmental deprivation, or even secondary to positive symptoms (2° to pos sxs) in schizophrenia. 

Although the usefulness of the atypical antipsychotics is best documented for the positive symptoms of schizophrenia, numerous studies are documenting the utility of these agents for the treatment of positive symptoms associated with several other disorders (discussed in Chapter 10 see Fig. 10—2). Atypical antipsychotics have become first-line acute and maintenance treatments for positive symptoms of psychosis, not only in schizophrenia but also in the acute manic and mixed manic-depressed phases of bipolar disorder in depressive psychosis and schizoaffective disorder in psychosis associated with behavioral disturbances in cognitive disorders such as Alzheimer s disease, Parkinson s disease, and other organic psychoses and in psychotic disorders in children and adolescents (Fig. 11—52, first-line treatments). In fact, current treatment standards have evolved in many countries so that atypical antipsychotics have largely replaced conventional antipsychotics for the treatment of positive psychotic symptoms except in a few specific clinical situations. 

Profound mood-stabilizing effects of the atypical antipsychotic drugs were observed once their antipsychotic effects were documented. These effects on mood appear to be quite independent of their effects on positive symptoms of psychosis. The most dramatic story may be how impressive the atypical antipsychotics are turning out to be for the treatment of bipolar disorder (Fig. 11 — 53). Although the best documented effect of these drugs is to reduce psychotic symptoms in the acute manic phase of bipolar disorder, it is clear that these agents also stabilize mood and can help in some of the most difficult cases, such as those marked by rapid cycling and mixed simultaneous manic-depressed states that are often nonresponsive to mood... 

Older classifications of psychiatric disorder divided diseases into psychoses and neuroses. The term psychosis is still widely used to describe a severe mental illness with the presence of hallucinations, delusions or extreme abnormalities of behaviour including marked overactivity, retardation and catatonia, usually accompanied by a lack of insight. Psychotic disorders therefore include schizophrenia, severe forms of depression and mania. Psychosis may also be due to illicit substances or organic conditions. Clinical features of schizophrenia may be subdivided into positive symptoms, which include hallucinations, delusions and thought disorder and negative symptoms such as apathy, flattening of affect and poverty of speech. 

Death from overdose of barbiturates may occur and is more likely when more than 10 times the hypnotic dose is ingested. The barbiturates with high lipid solubility and short half-lives are the most toxic. Thus the lethal dose of phenobarbital is 6—10 g, whereas that of secobarbital, pentobarbital, or amo-barbital is 2-3 g. Symptoms of barbiturate poisoning include CNS depression, coma, depressed reflex activity, a positive Babinski reflex, contracted pupils (with hypoxia there may be paralytic dilation), altered respiration, hypothermia, depressed cardiac function, hypotension, shock, pulmonary complications, and renal failure. 

O The goals of therapy for GAD are to acutely reduce the severity and duration of anxiety symptoms and restore overall functioning. The long-term goal in GAD is to achieve and maintain remission. With a positive response to treatment, patients with GAD and comorbid depression should have minimal depressive symptoms. 

In their next study, Mayberg and her colleagues scanned the brains of depressed patients who had responded positively to treatment for depression in a clinical trial of Prozac. The patients were scanned twice, once before the treatment had begun and once again after six weeks of treatment. About half of the patients responded positively to the treatment by showing at least a 50 per cent reduction in their symptoms the other half did not improve that much and were classified as non-responders. For the responders, but not for the non-responders, treatment of depression produced changes in brain activation in exactly the same areas in which normal sadness had produced changes, but in the opposite direction. In other words, successful treatment decreased brain activity in areas where sadness produces increased activity, and it increased brain activity in areas where sadness decreases it. 

Signs and Symptoms Fever, anorexia, depression, and incoordination (ataxia). Progressive paralysis, beginning in the hindquarters and ascending toward the head, may develop. In severe cases cannot rise from a dog-sitting position. Although animals that are mildly affected may recover, death usually results from paralysis of the respiratory muscles. 

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