Pharmacological treatment of anxiety in the medically ill patient.

Treatment guidelines which are available are intended for treatment of medically healthy patients. There is little information in the literature regarding the treatment of patients who are medically ill. Anxiety and anxiety disorders are frequently encountered in patients with serious medical disorders. These medically ill patients may have substantial changes in pharmacokinetic factors as a result of their current illness or treatment. Also, treatment considerations related to their accompanying medical treatment(s) are sometimes required. These various factors may result in a different initial choice of agents, alterations in the dosage of a given agent, or even preclude the use of some standard agents. In this chapter, we first present a review of the current psychopharmacologic treatment of anxiety disorders. In the second section, we review the potential pharmacokinetic consequences of serious hepatic renal, pulmonary and cardiac disease relevant to the pharmacological treatment of anxiety.     

Adverse consequences of fluoxetine-MAOI combination therapy

The authors describe two series of patients: 12 treated simultaneously with fluoxetine and a monoamine oxidase inhibitor and 6 patients started on treatment with an MAOI 10 days or more after stopping fluoxetine treatment. All patients had extremely refractory depression and were treated in open fashion before general knowledge was obtained of the side effects that may accompany the fluoxetine-MAOI combination. During the fluoxetine-MAOI trial, most patients continued to receive other psychotropic combinations that had been partially helpful. The use of fluoxetine and an MAOI, either together or in close succession, was accompanied by a very high incidence of adverse effects, especially the "serotonergic syndrome." This syndrome was characterized by mental status changes, such as hypomania and confusion, and physical symptoms, such as myoclonus, hypertension, tremor, and diarrhea. Because of the high incidence of side effects and the lack of definite efficacy, the concurrent use of fluoxetine and MAOIs should generally be avoided. The long half-lives of fluoxetine and norfluoxetine, as well as the prolonged metabolic effects of MAOIs, may also dispose patients to an interaction if one of the drugs is started soon after stopping the other.     

Stimulants in the treatment of depression: a critical overview

The authors reviewed the efficacy and safety of stimulant drugs in the treatment of depression. Although uncontrolled studies were generally positive, the 10 placebo-controlled studies of stimulant drugs in primary depression, with one exception, indicated little advantage of drug over placebo. Although several of these studies were methodologically unsophisticated, they were comparable with and performed during the same period as studies establishing the efficacy of imipramine. Controlled studies of stimulants in apathetic or depressed geriatric patients were more likely to be positive, but outcome frequently consisted of partial improvement. Studies in medically ill patients with depression were promising but uncontrolled. Side effects have not been severe, and these drugs may pose less of a risk than tricyclics in the medically ill or elderly. Habituation is suggested, but there are no placebo-controlled studies to confirm this. In short, the stimulant drugs do not appear to be as effective as the conventional antidepressants in primary depression, but may be of value in refractory cases or in special cases, such as those involving the medically ill patient. Placebo-controlled trials are needed to explore these questions.     

Predictors of depression in geriatric medically ill inpatients

OBJECTIVE: Depression in medically ill inpatients has been associated with increased morbidity and mortality. The purpose of this study was to identify variables that would successfully predict depression in this population. METHODS: The sample consisted of 314 male, medically ill veterans, age 60 and older, admitted to the acute medical service at Baltimore Veteran Administration Medical Center. Sixty of 314 patients met criteria for Major Depression and scored 11 or higher on the Geriatric Depression Scale. Variables assessing age, race, social support, severity of illness, degree of functional disability, life satisfaction, and hopelessness were included in a logistic regression analysis as predictors of depression. RESULTS: The variables that significantly predicted depression were derived from the Beck Hopelessness Scale, Life Satisfaction Score, and the Cumulative Illness Rating Score. CONCLUSIONS: The results indicated that medically ill inpatients who feel hopeless about the future, feel the best years of their lives are behind them, and have serious medical problems are likely to be clinically depressed.     

The use of methylphenidate in depressed patients after cardiac surgery

A positive therapeutic response to methylphenidate is described in four depressed patients who developed cardiovascular complications after cardiac surgery that contraindicated the use of tricyclic antidepressants. There was a rapid remission of depressive symptomatology with no adverse side effects. This observation is consistent with the findings of other investigators. Further evaluation of the therapeutic role of psychostimulants in the treatment of medically ill depressed patients is recommended.     

Thromboprophylaxis in non-surgical cancer patients

Acutely ill medical patients with cancer and cancer patients requiring non-surgical therapy are considered as non-surgical cancer patients and are at moderate to high risk of venous thromboembolism (VTE): approximately 10-30% of these patients may develop asymptomatic or symptomatic deep-vein thrombosis (DVT) or pulmonary embolism (PE), and the latter is a leading contributor to deaths in hospital. Other medical conditions associated with a high risk of VTE include cardiac disease, respiratory disease, inflammatory bowel disease, rheumatological and infectious diseases. Pre-disposing risk factors in non-surgical cancer patients include a history of VTE, immobilisation, history of metastatic malignancy, complicating infections, increasing age, obesity hormonal or antiangiogenic therapies, thalidomide and lenalidomide therapy. Heparins, both unfractionated (UFH) and low molecular weight heparin (LMWH) and fondaparinux have been shown to be effective agents in prevention of VTE in the medical setting with patients having a history of cancer. UFH and LMWH along with semuloparin also have a role in outpatients with cancer receiving chemotherapy. However, it has not yet been possible to demonstrate a significant effect on mortality rates in this population. UFH has a higher rate of bleeding complications than LMWH. Thromboprophylaxis has been shown to be effective in medical patients with cancer and may have an effect on cancer outcomes. Thromboprophylaxis in patients receiving chemotherapy remains controversial and requires further investigation. There is no evidence for the use of aspirin, warfarin or mechanical methods. We recommend either LMWH, or fondaparinux for the prevention of VTE in cancer patients with acute medical illnesses and UFH for those with significant severe renal impairment. For ambulatory cancer patients undergoing chemotherapy we recommend LMWH or semuloparin. These are safe and effective agents in the thromboprophylaxis of non-surgical cancer patients.     

Depression in the medically ill: an overview

Depressive symptoms and syndromes are common in the medically ill, although they are frequently unrecognized and untreated. The authors review the epidemiology, differential diagnosis, clinical presentations, and response to treatment of this clinical problem. They address such methodological issues in the current literature in this area as the advantages and limitations of standardized assessment measures and discuss treatment modalities for depression in the medically ill, including antidepressant medication and ECT. This clinical problem warrants attention for a variety of reasons: its prevalence, associated morbidity, and treatability. Elucidation of the mechanisms of depression in the medically ill may also contribute to a broader understanding of depression in other populations.     

Dysrhythmia associated with fluoxetine treatment in an elderly patient with cardiac disease

Although fluoxetine has been shown to be both efficacious and well tolerated, few data are available on the use of this drug in patients with preexisting heart disease and in the elderly. The authors report a case of an elderly patient in whom atrial fibrillation and bradycardia developed shortly after she began treatment with fluoxetine. The dysrhythmias recurred on rechallenge with the drug. A review of the pertinent literature is presented and possible pathophysiologic mechanisms are discussed.     

Fluoxetine-induced bradycardia and syncope in two patients

Fluoxetine appears to cause a low incidence of adverse cardiac effects. An uncommon but potentially hazardous effect of fluoxetine therapy, however, is bradycardia accompanied by faintness or syncope. The authors report two cases in which this adverse effect occurred. They hypothesize that the mechanism of bradycardia in these cases represents a direct central nervous system effect of increased serotonin on medullary cardiovascular regulation.     

The role of serotonin in sexual dysfunction: fluoxetine-associated orgasm dysfunction

Iatrogenic sexual dysfunction has been associated with many pharmacologic agents. The authors report 6 cases of orgasm dysfunction associated with the use of fluorxetine in 77 depressed outpatients. Fluoxetine is a novel antidepressant known to block the reuptake of serotonin with little effect on other neurotransmitter systems. Because fluoxetine has a specific mechanism of action, it serves as a useful model to hypothesize about potential mechanisms of drug-induced sexual dysfunction. The possible effects of serotonin on central, spinal, and peripheral anatomical areas are discussed in relation to drug-induced sexual dysfunction.     

Depression in the medically ill: diagnosis and treatment considerations in C-L psychiatry settings

Depression in general hospital patients is one of the main psychiatric problems in the medically ill. It often complicates the treatment and prognosis of patients with active medical conditions. However, depression in the medically ill is frequently under-recognized and under-treated. This article reviews the historical concept of secondary depression, and gives an overview of medical conditions and medications associated with depression. Phenomenological issues in the diagnosis of depression in medically ill populations and treatment considerations in C-L psychiatry settings will be discussed. The authors have used the examples of Parkinson's disease and epilepsy commonly associated with depression to illustrate how these considerations affect the C-L psychiatrist's choice of an antidepressant in the medically ill.     

Mania in the medically ill

Manic symptoms frequently occur in patients with comorbid medical disorders and present a diagnostic and treatment challenge. Manic symptoms may be due to an independent psychiatric illness, may be induced or precipitated by a medical condition, or may result from medication or substance use. The presence of manic symptoms in medically ill patients can lead to misdiagnosis or complicate the management of comorbid medical illness. It is of paramount importance to identify the etiology of the mania and, in particular, differentiate primary from secondary mania. Management of mania in the medically ill should focus on treating the underlying medical condition, medication management (antipsychotic agents, mood stabilizers, and/or benzodiazepines), and psychotherapy (if needed). Selecting appropriate medication for treatment requires basic knowledge of the pharmacokinetics of the medications, their side effect profile, and drug-drug interaction. The majority of deficits accompanying secondary mania resolve with treatment of the underlying cause, and supportive psychopharmacology may be all that is needed, but if symptoms persist, patients may need medications for a longer duration.     

Antidepressant side effects in the medically ill: the value of psychiatric consultation

In this study we evaluated the side effects of antidepressant use in medically ill patients. The authors evaluated fifty-one general hospital inpatients who were later prescribed antidepressant medications by their primary care physicians. These patients' medical records were reviewed one year later for evidence of serious complications. The overall complication rate was 43 percent. When the psychiatrist recommended antidepressant therapy, there was a 30 percent incidence of major complications. When the psychiatrist did not recommend antidepressants, but the patient was treated anyway, the incidence of treatment-limiting side effects was 67 percent. These results suggest that psychiatrists can predict which medically ill patients are at risk for complications. Since most antidepressants are prescribed by non-psychiatrists, an important role for consultants is to identify those patients at high risk for significant complications.     

The psychopharmacological treatment of depression in the medically ill patient

With the introduction of effective antidepressants, pharmacotherapy has not been limited exclusively to the psychiatrically ill, but has been expanded to include medically ill patients exhibiting depressive symptomatology as well. This has led to problems in diagnostic differentiation and, just as important, problems with interactions resulting from multiple medications. By describing the coexistence of depressive symptomatology in a large variety of physical illness, the physician is alerted to the complexities of psychiatric illness in the medically ill patient as well as the caution necessitated by the poly-pharmacotherapy required in this population.     

Supportive-expressive group psychotherapy for persons with inflammatory bowel disease.

OBJECTIVE: Supportive-expressive (SE) group psychotherapy is designed to be applicable to medically ill populations. In this open trial, SE therapy was adapted for use in treating inflammatory bowel disease (IBD). METHOD: Thirty subjects with Crohn's disease (CD) or ulcerative colitis (UC) were enrolled in 4 psychotherapy groups. Each group met weekly for 20 weeks to discuss emotional and interpersonal issues associated with illness. Physical and psychological variables were measured at the onset and at the finish of the group sessions. RESULTS: There was no mean group change in quality of life (QL), anxiety, or depression over the course of treatment, although there was a mean group reduction in maladaptive coping. CONCLUSION: Although the trial was uncontrolled and the sample size small, which limits interpretation, the results are consistent with an ineffective intervention. Because a null result would be consistent with previously reported psychotherapeutic trials in cases of IBD, and because SE therapy has been effective in treating other medically ill populations, we discuss characteristics of IBD that may account for a relative resistance to psychotherapeutic support.     

Methylphenidate in depressed medically ill patients

BACKGROUND: The purpose of the authors' study was to evaluate the efficacy of methylphenidate in the medically ill depressed patients and to examine the factors that appear to affect therapeutic response and side effects. METHOD: Hospital charts were reviewed for 29 patients who received trials of methylphenidate for treatment of depressive disorders while admitted to a medical/surgical unit. RESULTS: Of the 29 patients, 16 (55%) had moderate or marked improvement, all within 2 days of commencing treatment with the maximal dose. Of the 25 nondelirious patients, 16 (64%) had moderate or marked improvement, and the presence of delirium was significantly associated with decreased response. Therapeutic response was significantly correlated with maximum methylphenidate dose. Side effects were noted in 8 (28%) patients; most side effects were mild (tachycardia or agitation), and all reversed after the medication was discontinued. CONCLUSIONS: Methylphenidate provides a safe and effective alternative to tricyclic antidepressants in medically ill populations but appears to be less effective in the presence of delirium.     

Do people turn to religion in times of stress?: an examination of change in religiousness among elderly, medically ill patients

This study examined the effect of health-related stress on changes in religiousness in a sample of elderly, medically ill patients. Patients admitted to Duke University Medical Center (N = 745) were interviewed at baseline and 3-month follow-up. Increases in illness severity (from baseline to follow-up) were associated with decreases in both organizational and private religiousness at follow-up. Effect of illness severity on organizational religiousness was statistically mediated by changes in physical activity, while its effect on private religiousness remained significant after controlling for physical activity. These findings encourage further research investigating causal relationships between stress and religion, as well as identifying measures of religiousness that may capture this construct in the medically ill population.     

Assessment of depression in medically ill children presenting to pediatric specialty clinics

OBJECTIVE: Self-report measures of depression may be inaccurate when applied to medically ill children because of the overlap between medical and psychiatric symptoms. The American Academy of Pediatrics endorses the use of self-reports as diagnostic aids (used in patients who are suspected of having an emotional problem by their pediatricians). This approach has not been validated. We evaluated the diagnostic accuracy of the Children's Depression Inventory (CDI) in medically ill children who were referred for evaluation by their pediatricians. METHOD: The evaluation included the CDI and a best estimate diagnostic procedure that incorporated results from semistructured and other interviews. Evaluators were not aware of the CDI scores when making a diagnostic determination. RESULTS: One hundred twenty-five patients, 8-19 years old, were referred between September 2000 and May 2003. Eighty-one completed the diagnostic procedure. The CDI summary score performed well in identifying best estimate depressive disorder determinations in this cohort. A cutoff of 11 and above correctly identified 80% of cases, with a specificity of 70%. DISCUSSION: A self-report measure of depression (CDI) could be used as a diagnostic aid in medically ill children who are suspected of having an emotional problem by their pediatricians. This finding supports the "two-tier" depression screening approach endorsed by the American Academy of Pediatrics for use in pediatricians' offices.     

Avoiding psychotropic drug interactions in the cardiovascular patient

Recent advances in our understanding of the hepatic cytochrome P450 inhibitory effects of the newer antidepressants have increased concern about drug interactions in the practice of psychiatry. The authors summarize the potential interactions of psychoactive drugs with cardiovascular medications. Practicing psychiatrists encounter many patients with cardiovascular disease, and an awareness of these interactions will improve knowledgeable prescribing for medically ill patients with comorbid mental disorders.