Depression and bipolar disorder

Mood disorders, such as depression, Bipolar Disorder, and suicidal behaviors... 

Glueck et al. assessed hypocholesterolemia in 203 patients hospitalized with affective disorders (depression, bipolar disorder, and schizoaffective disorder), 1595 self-referred subjects in an urban supermarket screening, and 11,864 subjects in the National Health and Nutrition Examination Survey II (a national probability sample) [34], Low plasma cholesterol concentration (<160 mg/dL) was much more common in patients with affective disorders than in those found in urban supermarket screening subjects or in the National Health and Nutrition Examination Survey II subjects. When paired with supermarket screening subjects by age and sex, patients with affective disorders had much lower TC, LDL, HDL, and higher TG concentrations. However, there was no evidence that low plasma cholesterol could cause or worsen affective disorders [34]. 

Positron emission tomography (PET) is an important diagnostic technique using radiation (Fig.19.8). It employs radioisotopes such as (half-life 20.3 min) or (half-life 124 s) that emit positrons when they decay. These are incorporated (quickly, because of their short half-lives) into substances such as glucose, which are injected into the patient. By following the pattern of positron emission from the body, researchers can study blood flow and glucose metabolism in healthy and diseased individuals. Computer-reconstructed pictures of positron emissions from the brain are particularly useful, because the locations of glucose metabolism appear to differ between healthy persons and patients with ailments such as manic depression (bipolar disorder) and schizophrenia. 

A number of unapproved uses of antipsy- chotic drugs also exist. CPZ and haloperidol were used early on to treat phencyclidine (PCP)-induced psychosis. Psychoses associ- ated with depression, bipolar disorder, and Alzheimer s disease are commonly treated with haloperidol, risperidone, or olanzapine. Psychotic symptoms in Parkinson s disease patients caused by levodopa and/or dopaminergic agonists have been alleviated with quetiapine, because EPS-prone typical neuroleptics contraindicated in Parkinson s disease. 

Part II of the book outlines several mental-health diagnostic categories schizophrenia, mood disorders, depression, bipolar disorders, and specific anxiety disorders including generalized anxiety disorder and obsessive compulsive disorder. Each chapter provides a case example, consideration in diagnosis, and the interventions utilized. Medications used to treat these disorders and relevant psychosocial interventions are outlined. Each chapter emphasizes the need for accurate treatment planning and documentation and offers suggestions to facilitate this process. 

The following case studies are of patients with Alzheimer s disease, Parkinson s disease, depression, bipolar disorder and epilepsy. 

Drugs Used for Depression, Bipolar Disorders, and Attention Deficit Hyperactivity Disorder (ADHD)... 

These data show that for three psychotic disorders (schizophrenia, bipolar disorder and unipolar depression) the genetic contribution is over 50% but for reactive depression (in response to a traumatic life event ) and tuberculosis, an infectious disease caused by a species of Mycobacterium, environmental factors account for over 90% of the variance. 

Johnston-Wilson NLet al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 2000 5 142-149. 

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. 

Some, but not all, studies observe low CSF 5-HIAA in major depressive episodes. Numerous studies, though not all, have also reported no difference between patients with mania or depression in CSF 5-HIAA levels, consistent with both Prange et alls [15] permissive hypothesis for bipolar disorders and the indoleamine hypothesis. 

Another way that professionals assess for psychiatric disorders is to use an inventory that assesses for personality characteristics. The most famous of these inventories is the Minnesota Multiphasic Personality Inventory (MMPI), which is now in its second edition as an instrument. Although the MMPI is actually a personality inventory, as it names suggests, many professionals will use it to spot suspected psychiatric disorders, such as depression, Bipolar Disorder, Schizophrenia, and Anxiety Disorder. The MMPI has several scales to assess common personality traits, such as depression, mania, psychopathic deviance, and even alcohol and drug use (Weed, Butcher, McKenna, Ben-Porath, 1992). 

Lithium is the simplest therapeutic agent for the treatment of depression and has been used for over 100 years—lithium carbonate and citrate were described in the British Pharmacopoeia of 1885. Lithium therapy went through periods when it was in common use, and periods when it was discouraged. Finally, in 1949, J.J.F. Cade reported that lithium carbonate could reverse the symptoms of patients with bipolar disorder (manic-depression), a chronic disorder that affects between 1% and 2% of the population. The disease is characterized by episodic periods of elevated or depressed mood, severely reduces the patients quality of life and dramatically increases their likelihood of committing suicide. Today, it is the standard treatment, often combined with other drugs, for bipolar disorder and is prescribed in over 50% of bipolar disorder patients. It has clearly been shown to reduce the risk of suicide in mood disorder patients, and its socioeconomic impact is considerable—it is estimated to have saved around 9 billion in the USA alone in 1881. 

When is medication indicated in the treatment of psychiatric illness There is no short answer to this question. At one end of the continuum, patients with schizophrenia and other psychotic disorders, bipolar disorder, and severe major depressive disorder should always be considered candidates for pharmacotherapy, and neglecting to use medication, or at least discuss the use of medication with these patients, fails to adhere to the current standard of mental health care. Less severe depressive disorders, many anxiety disorders, and binge eating disorders can respond to psychotherapy and/or pharmacotherapy, and different therapies can target distinct symptom complexes in these situations. Finally, at the opposite end of the spectrum, adjustment disorders, specific phobias, or grief reactions should generally be treated with psychotherapy alone. 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

Neuropsychiatric events Life-threatening or fatal neuropsychiatric events, including suicide, suicidal and homicidal ideation, depression, relapse of drug addiction/overdose, and aggressive behavior have occurred in patients with and without a previous psychiatric disorder during peginterferon alfa-2b treatment and follow-up. Psychoses, hallucinations, bipolar disorders, and mania have been observed in patients treated with alpha interferons. 

Fatemi, S.H., Earle, J.A., and McMenomy, T. (2000) Reduction in reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol Psychiatry 5 654-653. 

Controlled studies involving lipid manipulation in children date back to the 1920s, when the ketogenic diet was pioneered to control treatment-resistant seizures in select pediatric populations (Freeman et al., 1998). However, no controlled evidence is available in children with depression, bipolar disorder, behavioral problems, or ADHD. In the absence of definite empirical data about effectiveness, treatment with EFA supplements should be considered unproven and patients ought to be advised accordingly. 

The primary indication for ECT in adolescents is the short-term treatment of mood symptoms, depressive or manic (Walter et al., 1999). Mood symptoms in the course of major depression, psychotic depression, bipolar disorder, organic mood disorders, schizophrenia, and schizoaffective disorder respond well to ECT. Psychotic symptoms in mood disorders also respond well to ECT whereas the effectiveness of ECT in the treatment of psychotic symptoms in schizophrenia is doubtful. There are suggestions that other uncommon clinical conditions in adolescents such as catatonia and neuroleptic malignant syndrome also benefit from ECT. The effectiveness of ECT seems to lessen when there is a comorbid personality disorder or drug and/or alcohol problems. There are very few data about usefulness on prepubertal children. 

Chart reviews and open trials of outpatients with bipolar disorder and bipolar spectrum disorder have been published for 28 risperidone- and 23 olanzapine-treated treated children and adolescents (Frazier et ah, 1999 2001). Significant decreases in mania, depression, and aggression ratings occurred over the course of treatment however, other medications were also used simultaneously. Additional anecdotal information exists for olanzapine (Soutullo et ah, 1999 Chang and Ketter, 2000), quetiapine (Schaller and Behar, 1999), and clozapine (Fuchs, 1994). 

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. 

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