Bipolar disorder psychoses

The electron-rich thiophene and benzothiophenes are widely used as isosteres of their phenyl cousins in medicinal chemistry. These ring systems can be found in many pharmaceuticals with varied therapeutic applications such as the inhibition of platelet aggregation, treatment of asthma, chronic obstructive pulmonary disorder (COPD), bipolar disorder, psychosis, and prevention of osteoporosis, among many others. ... 

Schizophrenia and bipolar disorder often share certain symptoms, including psychosis in some patients. The prominence of mood symptoms and the history of mood episodes distinguish bipolar disorder and schizophrenia. In addition, the psychosis of schizophrenia occurs in the absence of prominent mood symptoms. 

In clinical psychiatric terms, the affective disorders can be subdivided into unipolar and bipolar disorders. Unipolar depression is also known as psychotic depression, endogenous depression, idiopathic depression and major depressive disorder. Bipolar disorder is now recognised as being heterogeneous bipolar disorder I is equivalent to classical manic depressive psychosis, or manic depression, while bipolar disorder II is depression with hypomania (Dean, 2002). Unipolar mania is where periods of mania alternate with periods of more normal moods. Seasonal affective disorder (SAD) refers to depression with its onset most commonly in winter, followed by a gradual remission in spring. Some milder forms of severe depression, often those with an identifiable cause, may be referred to as reactive or neurotic depression. Secondary depression is associated with other illnesses, such as neuro-degenerative or cardiovascular diseases, and is relatively common. 

Bipolar disorder A group of affective disorders characterised by alternating periods of pathologically elevated moods, followed by severely reduced moods. Previously known as manic depression, or manic depressive psychosis. 

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. 

Shock Therapy. Insulin coma treatments were used in the early 1900s but offered no tangible improvement. Electroconvulsive therapy (ECT) arose in the 1930s and 1940s and was the hrst treatment to provide some relief from psychosis. However, its effects are only temporary and it proved too costly for continuous use. ECT continues to have some use for life-threatening catatonia, but it is mainly used to treat refractory depression or bipolar disorder. 

Psychosis or mania Antidepressants can precipitate manic episodes in bipolar disorder patients during the depressed phase of their illness and may activate latent psychosis in other susceptible individuals. The sustained-release formulation of bupropion is expected to pose similar risks. There were no reports of activation of psychosis or mania in clinical trials conducted in nondepressed smokers. 

Many of the children and adolescents seen for treatment of depression are experiencing their first depressive episode. Because the symptoms of unipolar and bipolar depression are similar, it is difficult to decide whether a patient needs only an antidepressant or concomitant use of mood stabilizers. As noted above, symptoms and signs such as psychosis, psychomotor retardation, or family history of bipolar disorder may warn the clinician about the risk of the child developing a manic episode. 

A potential limitation of most of the controlled studies discussed above relates to the numerous exclusion criteria used for patient selection. For example, in order to find homogenous samples, major depression, bipolar disorder, Tourette s disorder, psychosis (clomipramine, fluvoxamine and fluoxetine trials), primary psychiatric disorder other than OCD (clomipramine and sertraline trials), and attention deficit/hyperactivity disorder (ADHD), autism, or other developmental disorders (clomipramine and fluoxetine trials) were excluded. Thus it remains unknown how well these controlled studies will generalize to more naturalistic clinical populations that are highly comorbid and where exclusion criteria are not applied. 

These authors also examined which medications were prescribed to patients with specific diagnoses. The majority of antidepressants were prescribed for patients with major depression, dysthymia, or bipolar disorder. Antipsychotics were prescribed frequently for conduct/oppositional disorder, psychosis, and major depression or dysthymia. In the state hospital, the proportion of nonpsychotic patients who received antipsychotic treatment depended on patients age thus, the frequency of children who were not diagnosed with a psychotic disorder but who were treated with antipsychotic medication was greater among children 12 years and younger, in contrast to children ages 13 to 18 years. 

Given the available data, it is extremely important that clinicians evaluate patients with major depression for features of psychosis, because the failure to do so may result in inadequate treatment for the patient. A practical problem encountered by clinicians, however, is the subtlety of delusions. For example, it is not unusual in geriatric depression for patients to present with a somatic preoccupation that borders on delusional. These so-called near delusions may put the patient into the arena of psychotic depression. Some evidence exists that patients with depression with near delusions may respond more favorably to combinations of antidepressants and antipsychotics or ECT. Once the presence of both major depression and psychosis is determined, other psychotic disorders including bipolar disorder and schizophrenic spectrum illness must also be ruled out because this may influence long-term treatment decisions. 

The most common indications for antipsychotic drugs are the treatment of acute psychosis and the maintenance of remission of psychotic symptoms in patients with schizophrenia. More recently, the atypical antipsychotics have become part of the standard repertoire for the treatment of bipolar disorder, as discussed in Chapter 5. Antipsychotic drugs also ameliorate psychotic symptoms associated... 

Nonpsychotic persons also experience impaired performance as judged by a number of psychomotor and psychometric tests. Psychotic individuals, however, may actually show improvement in their performance as the psychosis is alleviated. The ability of the atypical antipsychotic drugs to improve some domains of cognition in patients with schizophrenia and bipolar disorder is controversial. Some individuals experience marked improvement and for that reason, cognition should be assessed in all patients with schizophrenia and a trial of an atypical agent considered, even if positive symptoms are well controlled by typical agents. 

FIGURE 10-5. Aggressive symptoms and hostility are associated with several conditions in addition to schizophrenia, including bipolar disorder, attention deficit hyperactivity disorder (ADHD) and conduct disorder (conduct dis.), childhood psychosis, Alzheimer s and other dementias, and borderline personality disorder, among others. 

Although aggressive symptoms are common in schizophrenia, they are far from unique to this condition. Thus, these same symptoms are frequently associated with bipolar disorder, childhood psychosis, borderline personality disorder, drug abuse, Alzheimer and other dementias, attention deficit hyperactivity disorder, conduct disorders in children, and many others (Fig. 10—5). 

This chapter will explore the various drug treatments for psychotic disorders, with special emphasis on schizophrenia. Such treatments include not only conventional antipsychotic drugs but also the newer atypical antipsychotic drugs, which are rapidly replacing the older conventional agents. We will also take a look into the future at the drugs under development for psychosis, especially schizophrenia. Mood stabilizers for bipolar disorders were covered in Chapter 7. 

Fig. 11—40) and clinical features, not only as compared with clozapine (Fig. 11 — 37) but also as compared with risperidone (Fig. 11—39)- Olanzapine is atypical in that it generally lacks EPS, not only at moderate doses but usually even at high doses. Thus, olanzapine tends to be used for some of the most difficult cases of schizophrenia, bipolar disorder, and other types of psychosis in which good control of psychosis without EPS is still desired, yet aggressive treatment is required. On the other hand, this approach can be very expensive. 

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... 

FIGURE 11-52. Positive symptom pharmacy. First-line treatment of positive symptoms is now atypical antipsychotics (SDA), not only for schizophrenia but also for positive symptoms associated with bipolar disorder, Alzheimer s disease, childhood psychoses, and other psychotic disorders. However, conventional antipsychotics (D2) and benzodiazepines (BZ) are still useful for acute intramuscular administration (in case of emergency), and D2 for monthly depot injections for noncompliant patients, as well as for second-line use after several atypical agents fail. Clozapine (C), polypharmacy, and combinations (combos) are relegated to second- and third-line treatment for positive symptoms of psychosis. 

The atypical neuroleptics—or new generation neuroleptics—cause fewer adverse side effects, are more effective in managing the symptoms of schizophrenia, and are effective for the treatment of bipolar disorder with or without psychosis. However, these drugs are cost more than the older medications. The five approved in the United States as of 2002 are ... 

---