Rational Polypharmacy Research Articles

(336/934): Clinical relationship between chronic pain and chronic combat related post traumatic stress disorder

Recent research and clinical practice suggest that there is strong interdependence between chronic pain and chronic post-traumatic stress disorder (PTSD), and there are several pathways by which both disorders may be involved in the escalation of symptoms and distress following trauma. The authors analysed the relationship between chronic pain and chronic combat-related PTSD among Croatian veterans. The 150 patients with chronic combat-related PTSD and chronic pain, who were treated at the Osijek University Clinical Hospital during year 2005, were selected as the sample for this study. On the base of clinical interviews, medical records and different self reported questionnaires (Mississippi Scale for combat-related PTSD, Mc Gill Pain Questionnaire, Pain Outcomes Questionnaire, Brief Pain Inventory, Beck Depression Inventory) the authors analysed the characteristics of chronic pain and PTSD, as well as pharmacological and non-pharmacological approaches that were used in the treatment. Combat veterans with PTSD reported in descending order back pain, headache pain, limb pain and torso pain. Intrusive symptoms of PTSD were significantly related to pain intensity and pain disability. Anxiety and depression were highly correlated to pain. All patients were treated with psychotropic drugs as well as with analgetics. The high levels of pain symptoms in PTSD patients suggests that pain is an important issue that needs to be recognized and treated by multidisciplinary approach. Rational polypharmacy may be essential to achieving and maintaining the full recovery of both disorders. But, pharmacotherapy alone is no sufficient to provide complete remission, and non-pharmacological methods have also very important place in the treatment of those patients.

Management of Neuropathic Pain

The concept of rational polypharmacy is now well established in the field of pain management. This concept has evolved in concert with progress in understanding the pathophysiologic mechanisms of pain diseases and disorders and how medications affect these processes. Other clinical factors must be considered in formulating the pain management strategy most likely to succeed in both controlling pain and improving function in a given patient. This article will review how pain diagnosis, pain mechanisms, pain phenomenology, medication efficacy, and risk profile influence medication selection in pain medicine practice, with a selective focus on the treatment of neuropathic pain. In addition, the role of psychosocial factors as they affect pain management will be discussed.

Symposium I

Symposium I

A Receptor-Based Paradigm of Nausea and Vomiting

AbstractNausea/vomiting remains a significant problem in medicine, especially in patients with chronic illnesses. The incidence and patient distress level from nausea/vomiting are underestimated by health care providers. A thorough patient evaluation followed by rational polypharmacy and a multimodal treatment approach may minimize the occurrence and intensity of nausea/vomiting. Utilizing new techniques (e.g., PET imaging of the CNS with novel radiotracers), clinicians may be better able to elucidate which receptors may be contributing to an individual's experience of nausea/vomiting and the relative importance of each. Future research into assessing precise mechanisms of nausea/vomiting in a particular patient may enable clinicians to design the most appropriate combinations of antiemetics in efforts to achieve the most effective therapy with the least side effects. Individually-tailored antiemetic “cocktails,” based on patient specific pathophysiology, may lead to optimal treatment outcomes.

Pain Science and Rational Polypharmacy

Pain Science and Rational Polypharmacy

Polypharmacy Treatment Approaches to the Psychiatric and Somatic Comorbidities Found in Patients with Chronic Pain

This review outlines the following: psychiatric and somatic comorbidities associated with chronic pain and their relationship to polypharmacy treatment, indications for polypharmacy in chronic pain, criteria for rational polypharmacy, basic principles of polypharmacy for pain-associated comorbidity, and, based on the above, psychopharmacologic polypharmacy treatment approaches to these chronic pain-associated comorbidities.

Monotherapy treatment of bipolar disorder with levetiracetam

Bipolar patients with early-onset, comorbid substance abuse, rapid cycling, and mixed episodes are difficult to treat and frequently require rational polypharmacy. When polypharmacy is unsuccessful, the clinician must consider the off-label use of newer psychotropics. Levetiracetam is a novel anticonvulsant with antikindling, inhibitory, and neuroprotective properties that is effective in an animal model of mania. This case report describes a patient with treatment-resistant rapid cycling bipolar disorder who failed 15 psychotropics, individually or in various combinations (maximum of 6), but ultimately responded to levetiracetam monotherapy and remained without bipolar features during 1 year of maintenance treatment, excluding 1 week during which the patient was medicine noncompliant. Further, methylphenidate used to treat comorbid attention deficit disorder did not precipitate manic features. Levetiracetam should be further studied for its potential use in the treatment of bipolar disorders.

Current pharmacological management of amyotropic lateral sclerosis and a role for rational polypharmacy

Current pharmacological management of amyotropic lateral sclerosis and a role for rational polypharmacy

Adjunctive oxcarbazepine in comorbid anxiety and affective disorder with hyponatremic seizure: case analysis and literature review*1

<h2>Abstract</h2> Rational polypharmacy is required for management of refractory psychiatric disorders. Antiepileptic drugs are increasingly used as primary or adjunctive agents in the treatment of affective, schizoaffective, anxiety, and impulse control disorders. In this case report, the authors present the first case of hyponatremic seizure associated with oxcarbazepine in adjunctive treatment of comorbid affective/anxiety disorders.

Adjunctive oxcarbazepine in comorbid anxiety and affective disorder with hyponatremic seizure: case analysis and literature review

Rational polypharmacy is required for management of refractory psychiatric disorders. Antiepileptic drugs are increasingly used as primary or adjunctive agents in the treatment of affective, schizoaffective, anxiety, and impulse control disorders. In this case report, the authors present the first case of hyponatremic seizure associated with oxcarbazepine in adjunctive treatment of comorbid affective/anxiety disorders.

Polypharmacy in Psychiatry

Back to table of contents Previous article Next article Book ReviewsFull AccessPolypharmacy in PsychiatryMichele L. Thomas, Pharm.D., B.C.P.P.Michele L. ThomasSearch for more papers by this author, Pharm.D., B.C.P.P.Published Online:1 Aug 2003https://doi.org/10.1176/appi.ps.54.8.1174AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail In general medicine, polypharmacy is a well-known and generally accepted practice that is often required in order to treat the complications of many disease states. Persons with asthma, for example, often require two or more inhalers as well as medication in tablet or capsule form for control of symptoms. In psychiatry, however, the practice of polypharmacy is generally considered to be taboo, and we are taught to avoid it or to use it only as a last resort in a patient's care. But just as asthma has many different causes, complications, and symptoms that need to be treated, so do psychiatric illnesses—maybe more so.Polypharmacy in Psychiatry is firmly grounded, thoughtfully written, and well balanced in its presentation and identification of the role of rational polypharmacy in psychiatry. S. Nassir Ghaemi, the book's editor, addresses many of the issues we struggle with on a daily basis and provides a comprehensive, well-rounded picture of the pros and cons of polypsychopharmacology.The book begins by addressing the origin of polypharmacy in psychiatry, dating back to the mid-19th century. The history of this "taboo" is explained in exquisite depth in the first chapter, whose authors set forth to review the practice of polypharmacy from its historical roots through the psychopharmacological revolution and to the present day. The book includes major reviews and offers much needed interdisciplinary insight into polypsychopharmacological issues pertaining to many of the major DSM diagnoses, such as schizophrenia, bipolar disorder, and posttraumatic stress disorder. Approaches to polypharmacy are discussed from the perspective of the disease, the type of drug, and the population—for example, high-risk populations, children, and medically compromised individuals. Issues surrounding "rational" as well as "irrational" polypharmacy are addressed in each of these contexts.Polypharmacy in Psychiatry is a well-referenced and unbiased presentation of much of today's issues of psychopharmacological care. Psychiatrists, pharmacists, nurses, social workers—anyone who works with psychotropic drugs—will benefit from this book. It gives a skillful overview of major controversies in psychopharmacological polypharmacy and summarizes much of the literature on current polypharmacy prescribing trends in psychiatry. Such a complete, detailed, and well-researched reference was long overdue in psychiatry.Dr. Thomas is a clinical psychopharmacologist at Central State Hospital in Petersburg, Virginia.edited by S. Nassir Ghaemi; New York, Marcel Dekker, 2002, 346 pages, $135 FiguresReferencesCited byDetailsCited ByNone Volume 54Issue 8 August 2003Pages 1174-1174 Metrics History Published online 1 August 2003 Published in print 1 August 2003

Treatment of Painful Peripheral Neuropathy

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Antidepressants and anticonvulsants are the two medication classes most widely studied and represent first-line agents in the management of neuropathic pain. The number of pharmacologic agents and interventional procedures that have shown effectiveness in the treatment of neuropathic pain continues to expand. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, because directed therapy can help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, because adverse events are common for many of these agents. Neuropathic pain management remains challenging because of heterogeneous responses between individuals and the fact that pain relief is rarely complete. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.

Combination of carbamazepine and valproate in different dose proportions in maximal electroshock seizure model in mice

Rational polypharmacy of antiepileptic drugs is one of the treatment strategies for refractory epilepsy. To investigate whether it may be rational to combine carbamazepine (CBZ) and valproate (VPA), we tested both the anti-convulsant effect and the toxicity of combinations of CBZ and VPA in different dose proportions. CBZ/VPA dose ratios were, respectively, 1:6.66, 1:10, 1:13.3 and 1:20. The median effect doses of monotherapy and polytherapy in maximal electroshock seizure test and the median lethal (within 3 days after administration) doses were determined. These parameters were analyzed with the isobologram method. We found that the anti-convulsant effect of all combinations was additive. The toxicity of combination 1, 2 and 3 (CBZ/VPA, 1:6.66, 1:10, 1:13.3) was additive, but the toxicity of combination 4 (CBZ/VPA, 1:20) was infra-additive. Thus, in mice, using this model, a combination of CBZ/VPA 1:20 has an advantage over each of the drugs alone.

Painful Peripheral Neuropathy.

Treatment of neuropathic pain is the primary focus of management for many patients with painful peripheral neuropathies. Neuropathic pain is a common feature of many peripheral neuropathies including those associated with diabetes, uremia, HIV infection, and alcohol abuse. Pain is also present in the majority of patients with idiopathic sensory and sensorimotor polyneuropathies. A growing number of pharmacologic agents are available for the treatment of neuropathic pain. The medications that have undergone the most rigorous study are the tricyclic antidepressants and anticonvulsants. These two families of medications are widely used and represent first-line agents in the management of neuropathic pain. Pain management should begin with a concerted effort to identify the etiology of the neuropathy, as directed therapy may help alleviate the symptoms. When initiating pharmacotherapy for neuropathic pain, one must individualize treatment and choose an agent that is likely to be tolerated, as adverse events are not uncommon for some of the medications. Treatment of neuropathic pain remains challenging, with considerable variability in an individual's response to the various agents and even to different drugs in the same class. However, monotherapy with a well-chosen agent or rational polypharmacy that combines medications with different mechanisms of action will benefit a majority of patients with neuropathic pain.

Psychopharmacology: rational and irrational polypharmacy.

Psychopharmacology: rational and irrational polypharmacy.

The pharmacologic basis of antiepileptic drug action.

The development of medications used in the treatment of epilepsy has accelerated over the past decade, and has benefited from a parallel growth in our knowledge of the basic mechanisms underlying neuronal excitability and synchronization. This understanding of the pharmacologic basis of antiepileptic drug (AED) action has, in large part, arisen from recent advances in cellular and molecular biology, coupled with avenues of drug discovery that have departed somewhat from the largely empiric approaches of the past. Physicians now have available to them an ever-growing armentarium of AEDs, necessitating a firmer appreciation of their mechanisms of action if more rational approaches toward both clinical application and research are to be adopted. An important example in this regard is the concept of rational polypharmacy for patients with epilepsy who are refractory to monotherapy. This review summarizes our current understanding of the molecular targets of clinically significant AEDs, comparing and contrasting their differing mechanisms of action.

Symptom-Focused Psychiatric Drug Therapy for Managed Care

Back to table of contents Previous article Next article Book ReviewFull AccessSymptom-Focused Psychiatric Drug Therapy for Managed CareNeil S. Kaye,, M.D.Neil S. Kaye,Search for more papers by this author, M.D.Published Online:1 Jun 1998https://doi.org/10.1176/ps.49.6.843AboutSectionsView EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail I must admit my bias: I was turned off by the title of this book. The notion that we should treat "symptoms" in order to further the cause of managed care is offensive. Although I run a busy, managed-care-friendly multidisciplinary mental health practice with six offices, I teach my residents that the bane of our profession is the "one symptom—one drug" thinking foisted on us by the pharmaceutical industry. Nonetheless, as I read the author's book, I tried to forgive him for trying to be timely and to appeal to the marketing forces where anything with "managed care" in the title is expected to sell; he has also writtenPersonality Disorders: New Symptom-Focused Drug Therapy1.The current book,Symptom-Focused Psychiatric Drug Therapy, has little new to offer the reader. It contains the largely anecdotal experience of one clinician and is sadly devoid of research findings to back up many of his assertions. The book is divided into two parts. In the first the author presents what is essentially a restatement of DSM-IVcriteria for each diagnosis and then a brief review of almost every medication known to have been tried for the disorder. He includes a list of the advantages and disadvantages of each compound. Unfortunately, they read like the slick marketing pamphlets of the pharmaceutical industry and again lack the substance that the reader would appreciate.Joseph also has an admitted tendency to lump together related but distinctly different classes of medications in way that any psychopharmacologist should eschew. An example is his inclusion of the tetracyclic compound maprotiline with the tricyclic antidepressants or his inclusion of venlafaxine as a selective serotonin reuptake inhibitor.The second part of the book contains 100 clinical cases, allegedly organized by degree of severity. Although earlier in the book Joseph argues for "rational polypharmacy," the cases presented reflect my initial fears. For most of these patients, at least one medication has been prescribed for each of their symptoms rather than an attempt being made to medicate the underlying disorder and then allow the symptoms to respond. This failure to see the patient as a whole is perhaps one of the greatest chimeras introduced to the medical world by managed care.In short, the book is best suited for a resident who might want to see what someone has tried. It is hoped that the resident would then ask himself or herself about the full conceptualization of the case and what else might be done to better assist the patient. Mixing numerous medications where another psychiatrist might hesitate to do so does not make one a psychopharmacologist. Reading the actual research journal articles and understanding the science should not be replaced by war stories, even when written by a well-known, published, and highly credentialed author. Other writings with treatment algorithms are far more useful and readily available to assist all of us as we attempt to treat patients most effectively and efficiently under the increasing pressures of managed care.Dr. Kaye is clinical assistant professor in the departments of psychiatry and family practice at Jefferson Medical College in Philadelphia and president of Allied Mental Health in Wilmington, Delaware.by S. Joseph, M.D., Ph.D., M.P.H.; Binghamton, New York, Haworth Medical Press, 1997, 510 pages, $89.95 hardcover, $24.95 softcover

Gabapentin potentiation of the antiepileptic efficacy of vigabatrin in an in vitro model of epilepsy.

1. An enhancement of promoted release of gamma-aminobutyric acid (GABA) and a change in GABA-metabolism have been suggested as mechanisms of action of gabapentin. Vigabatrin is supposed to act mainly via inhibition of GABA-transaminase but it also interferes with GABA-release and GABA-uptake. On the basis of these mechanisms of action, a pharmacodynamic interaction of the two antiepileptic drugs could be supposed which might be of relevance in the sense of a rational polypharmacy. 2. To address the aforementioned hypothesis, experiments were carried out on hippocampal slices (n=107) of guinea-pigs (n=70). Epileptiform field potentials (e.f.p.) were induced by omission of magnesium from the bath solution and recorded in the stratum pyramidale of the CA3 region. Gabapentin (30-600 microM; 5.1-102.72 microg ml(-1)), vigabatrin (50-200 microM, 6.45-25.8 microg ml(-1)) and the GABA(A)-receptor antagonist bicuculline (100 microM) were added to the bath solution for 3 h. 3. Gabapentin, in concentrations up to 600 microM, failed to decrease the repetition rate or duration of e.f.p. (n=19). However, vigabatrin, evoked a dose-dependent reduction of the repetition rate of e.f.p. For a concentration of 100 microM (12.9 microg ml(-1)) there was a reduction down to 48+/-5% (mean+/-s.e.mean) of the initial value within 3 h (n=11). With simultaneous administration of vigabatrin (100 microM) and gabapentin (60 microM) for 3 h (n=15), the repetition rate of e.f.p. decreased down to 8+/-3%, which is significantly different from the values obtained after administration of 100 microM vigabatrin alone (P<0.0001). Both, the antiepileptic effect of vigabatrin alone and the enhancement by gabapentin were blocked by the GABA(A)-receptor antagonist bicuculline (100 microM, n=16). 4. These results demonstrate that gabapentin is able to augment the antiepileptic effects of vigabatrin significantly. It is possible that a change in the GABA-release machinery is induced by vigabatrin which then can be augmented by gabapentin.

Rational Polypharmacy in Older Patients

Rational Polypharmacy in Older Patients

Meeting the challenge of epilepsy in persons with multiple handicaps.

Epilepsy occurs in more than 30% of persons with mental retardation and up to 50% of those with multiple handicaps living in institutional settings. Treatment of epilepsy in this population presents many unique challenges. Through careful adherence to basic principles of diagnosis, classification, and antiepileptic drug use, as many as 80% of individuals can be successfully managed with one- or two-drug therapy and enjoy positive outcomes in the areas of community integration and increased independence. Rational polypharmacy with the newer anticonvulsant drugs offers additional opportunity for improving outcomes for these individuals, especially with the use of felbamate and lamotrigine, where broad-spectrum efficacy and positive impact on psychosocial functioning is being demonstrated. Further systematic study of new drugs in this population is clearly warranted.