Anxiety Disorders: Medical Analysis

Summarize & explain the psychopharmacological interventions currently used for the anxiety disorders

Among the pharmacologic interventions for generalized anxiety disorders, a short course of a benzodiazepine is usually indicated, preferably lorazepam, oxazepam, or temazepam. They are started at the lowest possible dose and then depending on the symptoms, given on an as-needed basis. Benzodiazepines are not given for more than 4–6 weeks due to the risk of abuse and dependence, and the development of tolerance.

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Since relapses can occur, withdrawal of these drugs must be closely monitored; it can be done by a gradual, stepwise dose reduction (10% every 1–2 weeks) over a period of 6-12 weeks.

Before any attempt is made to discontinue the benzodiazepine, it is better to switch over to benzodiazepines with a longer half-life (diazepam, chlordiazepoxide, flurazepam, and clonazepam) or use an adjunctive medication, such as a beta-blocker or carbamazepine.

Other anxiolytic agents include buspirone, which is a nonbenzodiazepine drug. Although it is nonsedating, does not cause tolerance or dependence, has no abuse or disinhibition potential, and does not interact with benzodiazepine receptors or alcohol, it takes several weeks for the effect to occur and has to be given thrice daily.

Gabapentin, oxcarbazepine, tiagabine, pregabalin, and divalproex are anticonvulsants having GABAergic properties; these are also effective for anxiety (Reus, 1998.)

Describe the process of diagnosing schizophrenia and its subtypes

The diagnosis is made from clinical features. The condition begins in late adolescence, with an insidious (and less commonly acute) onset. There are no pathognomonic features (Reus, 1998). Patients may present with positive symptoms (conceptual disorganization, delusions, or hallucinations) or negative symptoms (loss of function, anhedonia, decreased emotional expression, impaired concentration, and diminished social engagement).

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In order to meet formal diagnostic criteria, patients must have at least two of these features for a month and continuous signs for at least 6 months. The four main subtypes of schizophrenia are catatonic, paranoid, disorganized, and residual (Reus, 1998). The diagnosis is principally one of exclusion, requiring the absence of significant associated mood symptoms, any relevant medical condition, and substance abuse. In patients with schizophrenia, although the general neurologic examination is usually normal, one-quarter of untreated patients may have motor rigidity, tremor, and dyskinesias (Reus, 1998.)

Compare and contrast the various impulse control disorders and the current thought as regards pharmacological treatment of those disorders

Impulse control disorders includes intermittent explosive disorder, kleptomania, pyromania, pathological gambling, and trichotillomania.

Kleptomania is characterized by include an inability to resist an impulse to steal, and a sense of pleasure or satisfaction after the act. It is usually seen in late adolescence or early adulthood, and more common in females.

Pathological gambling is “characterized by persistent and recurrent maladaptive patterns of gambling behavior”. In contrast to kleptomania, it begins in early adulthood, and more common in males.

Trichotillomania is characterized by purposeful pulling of one’s own hair along with functional impairment or distress. Like kleptomania, the onset is during adolescence and more common in females (Grant & Potenza, 2006.)

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Pyromania is an impulse to set fires with a sense of pleasure or satisfaction after the act. It is more common in children and adolescents and in males (Encyclopedia of Mental Disorders, 2007.)

Intermittent explosive disorder is characterized by episodes of unneeded anger, and the person may cause bodily injury to others or damage property. Like pyromania, the condition begins in the early teens, and is more common in men (NIMH, 2006.)

The choice of treatment for pathological gambling is not clear; similarly, the efficacy of SRIs (serotonin reuptake inhibitors) for trichotillomania is not convincing, although there are positive results from clinical trials with lithium and naltrexone (Grant & Potenza, 2006). Serotonin Specific Reuptake Inhibitors (SSRIs) could be effective in the treatment of kleptomania (Lepkifker et al., 1999). Treatment for pyromania in adults is selective serotonin reuptake inhibitors with psychotherapy, while in children it is psychotherapy (Encyclopedia of Mental Disorders, 2007). For intermittent explosive disorder, anticonvulsants (carbamazepine), anti-anxiety agents (benzodiazepine), mood regulators (lithium) and antidepressants (fluoxetine) may be useful

Describe personality disorders and discuss the rationale for using psychopharmacological intervention in those disorders

“Personality disorders are characteristic patterns of thinking, feeling, and interpersonal behavior that are relatively inflexible and cause significant functional impairment or subjective distress for the individual” (Reus, 1998.) Personality disorders are not secondary to another mental disorder, nor are they precipitated by substance abuse or a general medical condition.

The pharmacological treatment for cluster A personality disorders includes antidepressants and low-dose antipsychotics. For cluster B patients with marked mood reactivity, behavioral dyscontrol, and/or rejection hypersensitivity, anticonvulsant mood-stabilizing agents and MAOIs may be beneficial. Cluster C patients may benefit with medications used for axis I anxiety disorders (Reus, 1998.)

Differentiate between medications and medical conditions, which simulate psychiatric disorders

Psychiatric symptoms may be caused by alcohol and other drugs (AODs). To differentiate between the two, it is necessary to obtain a thorough history of AOD use. One important feature of AOD abuse is the presence of dysfunction related to the patient’s AOD use. Proper screening questions can reveal AOD abuse (Ries, 2007.)

Medical illnesses presenting as psychiatric syndromes include: systemic lupus erythematosus, multiple sclerosis, seizure disorders, and degenerative central nervous system diseases (Goldman, 2000). A careful history and clinical examination will reveal any underlying medical condition.

Explain the basic principles of diagnosis and treatment

There are many formal and informal systems for categorizing mental disorders. The Diagnostic and Statistical Manual of Mental Disorders (DSM) is one of them. By collecting assessment data during a patient interview, the physician determines if the patient meets the diagnostic criteria for a particular mental disorder (Sommers-Flanagan, 2002). However, DSM is only meant to be a guide. A balanced diagnostic interview consists of: a review of standardized questionnaires, review of the client’s problems and symptoms, a brief discussion of the client’s personal experiences including a history of the presenting problem, a brief mental status examination, and a review of the client’s current situation, including social support network, coping skills, physical health etc.

Treatment plans are of two types: psychosocial treatment planning and medical treatment planning. Psychosocial treatment planning is characterized by a greater emphasis on identification of the client’s problems and a lesser emphasis on establishing a definitive psychiatric diagnosis. Medical treatment planning involves performing diagnostic assessments of the client’s and then recommending specific treatment interventions (Sommers-Flanagan, 2002.)

Analyze the biological basis of psychopharmacology, including neurotransmitters

Nerve cells are the basic functional unit of the nervous system, and in the brain, neurons communicate with each other at the synapses (a narrow gap separating two neurons) (Thomas, Hardy et al., 1997). During the process of neurotransmission, the storage vesicle in the presynaptic cell releases a chemical neurotransmitter.

After the neurotransmitter crosses the synapse, it acts on the receptor on the postsynaptic cell membrane. Here, it may either act as a receptor activator (agonist) or very rarely, as an inhibitor (antagonists), thereby triggering complex responses inside the cell (Thomas, Hardy et al., 1997). The remaining neurotransmitter in the synapse is either reabsorbed (reuptake) and stored by the presynaptic cell or is metabolized (inactivated) by enzymes like monoamine oxidase (MAO).

Some examples of neurotransmitters include noradrenaline, acetylcholine, gamma-aminobutyric acid (GABA), dopamine, and 5-hydroxytryptamine (5-HT or serotonin).

Most of the psychiatric disorders are believed to be due to either an under-response or an over response at any point in the neurotransmission process. An excessive neurotransmission of dopamine, for example, can result in psychosis (Thomas, Hardy et al., 1997). Any disruption of the neurotransmission of noradrenaline, serotonin, and other neurotransmitters can lead to depression and mania, while the dysregulation of GABA and endogenous antianxiety chemicals can result in anxiety.

Pharmacological strategies in psychiatry involve affecting the cell-to-cell communication at the synapse. Drugs can either release more neurotransmitters into the synapse, block neurotransmitters binding to the postsynaptic receptor, make the receptor more or less responsive to the neurotransmitters, block reuptake of neurotransmitters, or interfere with storage vesicles.

Antipsychotic drugs block dopamine from the receptor site; tricyclic antidepressants and serotonin reuptake inhibitors (SSRIs) block the reuptake of noradrenaline and serotonin; MAO inhibitors (MAOIs) prevent enzymatic metabolism of noradrenaline and serotonin; benzodiazepines potentiate GABA (Thomas, Hardy et al., 1997).

8. Describe the three clusters of personality disorders along with the natural history, epidemiology, and genetics of the disorders as a preliminary knowledge base leading to an understanding of the psychopharmacologic treatment of specific personality disorders

Personality disorders are grouped into three clusters; clusters A, B and C. Cluster A (includes paranoid, schizoid, and schizotypal personality disorders).

Individuals belonging to this group are odd and eccentric and maintain an emotional distance from others. They are isolated socially. Paranoid personality disorder is characterized by “a pervasive mistrust and suspiciousness of others to an extent that is unjustified by available evidence” (Reus, 1998). A patient having “unusual perceptual experiences and express magical beliefs about the external world” characterizes schizotypal personality disorder.

Cluster B (includes antisocial, borderline, histrionic, and narcissistic types). These individuals are impulsive, excessively emotional, and erratic in nature.

Cluster C (includes avoidant, dependent, and obsessive-compulsive personality types). These individuals have excess anxiety and fear (Reus, 1998.)

Natural history of personality disorders-traditionally, personality disorders (PD) has been thought to be of long duration, with an onset in adolescence or early adulthood. PD tends to improve over time. Personality psychopathology fluctuates depending on the circumstances of a person’s life.

Epidemiology of PD-not much is known about the prevalence of personality disorders, because very few studies have been performed that represent the general population. In general, the prevalence varies from 3.9 % and 22.7%. The median prevalence is 11.55% (Oldham, Skodol, Bender, 2005.) As far as gender is concerned, men have a higher prevalence of personality disorders. Older people have higher prevalence of schizoid personality disorder and obsessive-compulsive disorder, while younger people have higher prevalence of passive-aggressive personality disorder, antisocial and borderline disorder, and histrionic and narcissistic disorders.

Genetics of PD-there is clear evidence for moderate heritability of schizotypal PD and antisocial PD (Oldham, Skodol, Bender, 2005.)

Compare and contrast the action of cyclic antidepressants

Tricyclic antidepressants are used for severe depression or depression that occurs with anxiety. They are compared and contrasted below:

Drug Comparison
1.Imipramine, Desipramine, Nortriptyline
2.Desipramine, Nortriptyline
All three cause continued improvement for several months. Not very helpful for anticipatory anxiety.
Response requires weeks or months. Increases sensitivity to the sun. Helpful for depression as well as panic.
Contrast
Imipramine

Nortriptyline
Amitriptyline

-Initial use of imipramine occasionally causes an increase in anxiety. Anticholinergic effects are stronger than most other antidepressants.

-Less jitteriness than imipramine. Less postural hypotension than other tricyclic antidepressants.
-Less potential for insomnia.

Describe the antidepressant classes, prescribing techniques and side effects of the SSRI’s, novel antidepressants, tricyclic antidepressants, and MAO inhibitors

Antidepressants can be classified into the following:

  1. Monoamine oxidase (MAO) inhibitors-phenelzine
  2. Cyclic antidepressants-imipramine, nortriptyline, amitriptyline etc.
  3. Lithium carbonate
  4. Caffeine like drugs.
  5. Selective serotonin reuptake inhibitors (SSRI)- citalopram, escitalopram, fluoxetine, paroxetine, sertraline.

At least 60 to 70% of patients respond to any antidepressant if given in a sufficient dose for at least 6–8 weeks. In the process of selecting an antidepressant, one rational approach is to match the patient’s preference and medical history with the metabolic and side effect profile of the drug.

The choice of a specific antidepressant could depend on the previous response or a family history of a positive response to the drug. The physician should also evaluate the contribution of comorbid illnesses and consider their specific treatment before starting antidepressant therapy (Reus, 1998). Treatment is started at 1/3 or ½ target dose if the drug is TCA or full dose as tolerated if it is SSRI. If side effects are present, the drug is tapered over a week and a new trial is initiated.

The response is evaluated after 6 weeks at target dose; if the response is inadequate, the dose is increased in a stepwise manner as tolerated (Reus, 1998). If the response is inadequate even after maximal dose, then the drug is tapered or a new drug is chosen. Regardless of the treatment undertaken, the response should be evaluated after 2 months.

MAOIs should not be used along with SSRIs due to the risk of serotonin syndrome, or with TCAs, due to hyperadrenergic effects (Reus, 1998.)

Side effects of SSRI include: headache, nausea, sexual problems, nervousness, agitation, and insomnia. The most common side effects of tricyclic antidepressants include: tachycardia, dry mouth, constipation, bladder problems, sexual problems, blurred vision, drowsiness, and dizziness (NIMH, 2008).

Explain the specific biologic effects, clinical uses, food and drug interactions, and other side effects of the MAO inhibitors

As neurotransmitters are released into the synaptic space, they are reabsorbed into the proximal nerve where they get metabolized by the enzyme monoamine oxidase (MAO) (Marcus, 2008). In the brain, MAO inhibitors (MAOIs) blocks MAO from metabolizing the neurotransmitters serotonin, dopamine, and norepinephrine, thereby increasing the levels of these neurotransmitters and elevating the mood (MayoClinic.com, 2008). While older MAOIs (phenelzine, isocarboxazid, and tranylcypromine) are nonselective inhibitors, the newer MAOIs are selective inhibitors of either MAOI-A or MAOI-B (Reus, 1998.) MAOIs may have drug interactions with serotonin reuptake inhibitors, several analgesics (particularly meperidine), and tyramine-containing foods (aged cheeses, aged, pickled, or smoked meats, yeast extracts, beer, red wine etc).

Any catecholamine-releasing drug can cause life-threatening events in patient’s who also use MAOIs (Marcus, 2008). Common side effects of MAOIs include orthostatic hypotension, weight gain, insomnia, and sexual dysfunction (Reus, 1998.)

Analyze the clinical uses and biologic effects of Lithium and the various side effects of lithium therapy

Lithium carbonate is the mainly used in the treatment of bipolar disorder. Lithium also has a prophylactic effect in prevention of recurrent mania, and to a lesser extent, in the prevention of recurrent depression.

Lithium may exert its therapeutic benefit through a resynchronization of intrinsic rhythms keyed to the light/dark cycle (Reus, 1998). Common side effects of lithium include: nausea, anorexia, diarrhea, fine tremor, thirst, polyuria, fatigue, weight gain, acne, folliculitis, neutrophilia, and hypothyroidism (Reus, 1998.)

Summarize the history and clinical uses, the biologic effects and techniques for prescribing the antipsychotics

It was Paul Ehrlich, in 1891, who discovered the antimalarial effects of methylene blue, a phenothiazine derivative. In 1951, the aliphatic phenothiazine, chlorpromazine, was given to patients for its anesthetic effects during surgery (Shen, 1999). Later, this treatment was tried in psychiatric patients, when its antipsychotic effects were first observed. From the years 1954 to 1975, as many as 15-40 antipsychotic drugs were introduced. In 1990, clozapine was introduced in U.S (Shen, 1999). This drug demonstrated efficacy for the negative symptoms of schizophrenia, and in treatment-refractory patients. It also did not elevate prolactin levels after chronic use (Shen, 1999)

Antipsychotic agents are the main drug of choice for acute and maintenance treatment of schizophrenia. They are effective in the treatment of hallucinations, delusions, and thought disorders, irrespective of the etiology.. The mechanism of action involves binding to dopamine D2/D3 receptors in the ventral striatum.

However, the clinical efficacy of newer atypical neuroleptics may involve NMDA receptor blockade, alpha1 and alpha2 noradrenergic activity, altering the relationship between 5HT2 and D2 receptor activity, as well as faster dissociation of D2 binding and effects on neuroplasticity (Reus, 1998). First-generation antipsychotics include: chlorpromazine, thioridazine, haloperidol etc. Second-generation antipsychotics include: risperidone, olanzapine etc.

The choice of antipsychotics depends mainly on the side-effect profile and cost of treatment or on a past personal or family history of a favorable response to the specific drug (Reus, 1998). Atypical agents appear to be more effective in treating negative symptoms and improving cognitive function. An equivalent treatment response can usually be achieved with relatively low doses of any drug selected (4–6 mg/d of haloperidol, 10–15 mg of olanzapine, or 4–6 mg/d of risperidone) (Reus, 1998). Maintenance treatment requires careful attention to the possibility of relapse and monitoring for the development of a movement disorder. Intermittent drug treatment is less effective than regular dosing, but gradual dose reduction is likely to improve social functioning in many schizophrenic patients who have been maintained at high doses (Reus, 1998.) Improvement may be observed within hours or days, but full remission usually requires 6–8 weeks. However, the relapse rate is 60% within 6 months if the medications are completely discontinued.

Long-acting injectable preparations (risperidone) are considered when noncompliance with oral therapy leads to relapses. In treatment-resistant patients, a transition to clozapine usually results in rapid improvement, but a prolonged delay in response in some cases necessitates a 6- to 9-month trial for maximal benefit to occur (Reus, 1998.)

14. Summarize the issues implicit in treating the following special populations: children, adolescents, the elderly, and women of childbearing and lactating capacity. In addition to the above special populations, consider the recovering individual whose need for psychopharmacologic intervention may come into conflict with recovery

Medication use during pregnancy is associated with teratogenicity, perinatal syndromes (neonatal toxicity), and postnatal behavioral sequelae. Although the absolute risk of congenital malformations after the use of most psychotropics in the prenatal period is low, first-trimester exposure to low-potency phenothiazines, lithium, certain anticonvulsants, and benzodiazepines may increase the relative risk for congenital anomalies (Altshuler, Cohen et al., 1997).

Psychotropics that can be used during pregnancy include: tricyclic antidepressants, fluoxetine. Lithium is the drug of choice after fetal echocardiography and ultrasonography are done (Arnon, Shechtman, Ornoy, 2000.) Most psychotropics are secreted in breast milk only at low concentrations, and thus, breastfeeding is possible, although the nursing should be discontinued if the infant shows clinical side effects (Arnon, Shechtman, Ornoy, 2000.)

In children, adolescents and elderly patient’s requiring treatment, the first choice of treatment is SSRIs (Emslie & Judge, 2000.)

Describe the side effects of antipsychotic therapy, specifically: dystonic reactions, akinesia, akathesia, neuroleptic malignant syndrome, as well as the non-neurologic side effects, tardive dyskinesia

Antipsychotic medications can cause a wide range of side effects, including lethargy, weight gain, postural hypotension, constipation, and dry mouth (Reus, 1998). Extrapyramidal symptoms such as dystonia (prolonged and unintentional muscular contractions of voluntary or involuntary muscles), akathisia (subjective sense of restlessness, with objective evidence of restlessness like pacing or rocking), and akinesia are also frequent with first-generation agents.

In rare cases, more serious and occasionally life-threatening side effects may emerge, including ventricular arrhythmias, gastrointestinal obstruction, retinal pigmentation, obstructive jaundice, and neuroleptic malignant syndrome (characterized by hyperthermia, autonomic dysfunction, muscular rigidity, and elevated creatine phosphokinase levels). The most serious adverse effects of clozapine are agranulocytosis (Reus, 1998.)

Clozapine, olanzapine, and quetiapine are more likely to cause hyperglycemia, weight gain, and hypertriglyceridemia (Reus, 1998). A serious side effect of long-term use of first generation antipsychotic agents is tardive dyskinesia (abnormal, unintentional choreoathetoid movements of the head, limbs, and trunk) (Kamin, Manwani, Hughes, 2000). Most of the neurological side effects of antipsychotics are due to the antidopaminergic effect in the caudate nucleus and other basal ganglia nuclei (Kamin, Manwani, Hughes, 2000.)

References

Anxieties.com (n.d). Tricyclic Antidepressants (TCAs). 2008. Web.

Altshuler LL, Cohen L, Szuba MP, Burt VK, Gitlin M, Mintz J (1996). Antidepressants During Pregnancy and Breastfeeding. Am J Psychiatry. May;153(5):592-606.

Arnon J, Shechtman S, Ornoy A (2000). The use of psychiatric drugs in pregnancy and lactation.Isr J Psychiatry Relat Sci. 2000;37(3):205-22.

Encyclopedia of Mental Disorders. Pyromania. 2008. Web.

Emslie G, Judge R (2000). Tricyclic antidepressants and selective serotonin reuptake inhibitors: use during pregnancy, in children/adolescents and in the elderly. Acta Psychiatr Scand Suppl;403:26-34.

Grant, JE, Potenza, MN (2006). Compulsive Aspects of Impulse-Control Disorders. Psychiatr Clin North Am. 2006; 29(2): 539.

Goldman, HH (2000). Review of General Psychiatry. McGraw-Hill Professional.

Kamin, J, Manwani, S, Hughes, D (2000). Emergency Psychiatry: Extrapyramidal Side Effects in the Psychiatric Emergency Service. Psychiatr Serv 51:287-289.

Lepkifker E, Dannon PN, Ziv R, Iancu I, Horesh N, Kotler M (1999). The treatment of kleptomania with serotonin reuptake inhibitors. Clin Neuropharmacol. 22(1):40-3.

MayoClinic.com (2008). Intermittent explosive disorder. Web.

MayoClinic.com (2008). Monoamine oxidase inhibitors (MAOIs). Web.

Marcus, S (2008). Emedicine. Toxicity, Monoamine Oxidase Inhibitor. Web.

NIMH (2006). Intermittent Explosive Disorder Affects up to 16 Million Americans. Web.

NIMH (2008). Medications. Web.

Oldham, JM, Skodol, AE, Bender, DS (2005). The American Psychiatric Publishing Textbook of Personality Disorders. American Psychiatric Pub.

Ries, RK (2007). Dual Disorders: Concepts and Definitions. Psych Central. Web.

Reus, VI (1998). Mental disorders. Harrison’s Principles of Internal Medicine. McGraw-Hill.

Sommers-Flanagan, J (2002). Clinical Interviewing. John Wiley and Sons.

Shen WW (1999). A history of antipsychotic drug development. Compr Psychiatry: 40(6):407-14.

Thomas, B, Hardy, S, Cutting, P, Gail (1997). Stuart and Sundeen’s mental health nursing: Principles and Practice. Elsevier Health Sciences.

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