Pharmacotherapy Of Mood Disorders Research Articles

Where Does Lamotrigine Fit in the Pharmacotherapy of Mood Disorders? An Evidence-Based Appraisal.

Where Does Lamotrigine Fit in the Pharmacotherapy of Mood Disorders? An Evidence-Based Appraisal.

Is there a future for other glutamate receptor modulators in the pharmacotherapy of mood disorders?

There is increasing evidence that some glutamatergic drugs could have antidepressant effects. Ketamine as a promising prototype for novel glutamatergic antidepressants has a much faster onset of action and is...

Drs Aprahamian and Forlenza Reply

Article Abstract Because this piece does not have an abstract, we have provided for your benefit the first 3 sentences of the full text. To the Editor: In his letter commenting on our recent article, Dr Lozano accurately reinforced the risk of renal and neurologic complications secondary to chronic lithium use. These adverse events are well known to most clinicians and have been clearly reported in the medical literature. Nonetheless, the use of lithium salts still represents an important strategy for the treatment of complex neuropsychiatric disorders, namely bipolar disorder, which invariably requires long-term management. Lithium represents a first-line therapeutic strategy or an adjunctive approach in the pharmacotherapy of mood disorders.

Pharmacotherapy for Mood Disorders in Pregnancy

Pharmacotherapy for mood disorders during pregnancy is often complicated by pregnancy-related pharmacokinetic changes and the need for dose adjustments. The objectives of this review are to summarize the evidence for change in perinatal pharmacokinetics of commonly used pharmacotherapies for mood disorders, discuss the implications for clinical and therapeutic drug monitoring (TDM), and make clinical recommendations. The English-language literature indexed on MEDLINE/PubMed was searched for original observational studies (controlled and uncontrolled, prospective and retrospective), case reports, and case series that evaluated or described pharmacokinetic changes or TDM during pregnancy or the postpartum period. Pregnancy-associated changes in absorption, distribution, metabolism, and elimination may result in lowered psychotropic drug levels and possible treatment effects, particularly in late pregnancy. Mechanisms include changes in both phase 1 hepatic cytochrome P450 and phase 2 uridine diphosphate glucuronosyltransferase enzyme activities, changes in hepatic and renal blood flow, and glomerular filtration rate. Therapeutic drug monitoring, in combination with clinical monitoring, is indicated for tricyclic antidepressants and mood stabilizers during the perinatal period. Substantial pharmacokinetic changes can occur during pregnancy in a number of commonly used antidepressants and mood stabilizers. Dose increases may be indicated for antidepressants including citalopram, clomipramine, imipramine, fluoxetine, fluvoxamine, nortriptyline, paroxetine, and sertraline, especially late in pregnancy. Antenatal dose increases may also be needed for lithium, lamotrigine, and valproic acid because of perinatal changes in metabolism. Close clinical monitoring of perinatal mood disorders and TDM of tricyclic antidepressants and mood stabilizers are recommended.

C.10.03 Where do we go from here? Pharmacotherapy of mood disorders

C.10.03 Where do we go from here? Pharmacotherapy of mood disorders

The hidden third: improving outcome in treatment-resistant depression

Treatment-resistant depression (TRD) presents many challenges for both patients and physicians. This review aims to evaluate the current status of the field of TRD and reflects the main findings of a consensus meeting held in September 2009. Literature searches were also conducted using PubMed and EMBASE. Abstracts of the retrieved articles were reviewed independently by the authors for inclusion. Evaluation of the clinical evidence in TRD is complicated by the absence of a validated definition, and there is a need to move away from traditional definitions of remission based on severity of symptoms to one that includes normalisation of functioning. One potential way of improving treatment of TRD is through the use of predictive biomarkers and clinical variables. The advent of new treatments may also help by focusing on neurotransmitters other than serotonin. Strategies such as the switching of antidepressants, use of combination therapy with lithium, atypical antipsychotics and other pharmacological agents can improve outcomes, and techniques such as deep brain stimulation and vagus nerve stimulation have shown promising early results. Despite consistent advances in the pharmacotherapy of mood disorders in the last decade, high rates of TRD are still a challenging aspect of overall management.

Sexual Dysfunction, Depression, and the Impact of Antidepressants

Sexual dysfunction is a common symptom of depression. Although decreased libido is most often reported, difficulties with arousal, resulting in vaginal dryness in women and erectile dysfunction in men, and absent or delayed orgasm are also prevalent. Sexual dysfunction is also a frequent adverse effect of treatment with most antidepressants and is one of the predominant reasons for premature drug discontinuation. Selective serotonin reuptake inhibitors are the most widely prescribed antidepressants and have significant effects on arousal and orgasm compared with antidepressants that target norepinephrine, dopamine, and melatonin systems. The availability of an antidepressant that does not cause or exacerbate sexual dysfunction represents an advance in pharmacotherapy for mood disorders and should reduce treatment noncompliance and decrease the need for switching antidepressants or adding antidotes. The purpose of this review was to provide an update on the prevalence, psychobiology, and relative adverse effect burden of sexual dysfunction associated with different antidepressants.

Is major depressive disorder a metabolic encephalopathy?

Metabolic encephalopathy is an acute disturbance in cellular metabolism in the brain evoked by conditions of hypoxia, hypoglycaemia, oxidative stress and/or inflammation. It usually develops acutely or subacutely and is reversible if the systemic disorder is treated. If left untreated, however, metabolic encephalopathy may result in secondary structural damage to the brain. Most encephalopathies are present with neuropsychiatric symptoms, one in particular being depression. However, mood disorders are often co-morbid with cardiovascular, liver, kidney and endocrine disorders, while increasing evidence concurs that depression involves inflammatory and neurodegenerative processes. This would suggest that metabolic disturbances resembling encephalopathy may underscore the basic neuropathology of depression at a far deeper level than currently realized. Viewing depression as a form of encephalopathy, and exploiting knowledge gleaned from our understanding of the neurochemistry and treatment of metabolic encephalopathy, may assist in our understanding of the neurobiology of depression, but also in realizing new ideas in the pharmacotherapy of mood disorders.

Pharmacotherapy of Mood Disorders

The mood disorders-primarily major depressive disorder and bipolar affective disorder-constitute one of the world's greatest public health problems and are associated with significant reductions in productivity, health, and longevity. In addition, people who suffer from these common illnesses, along with their families and loved ones, experience an incalculable toll on quality of life. Dating to the introduction of the first effective therapies for mood disorders in the late 1950s and 1960s, various types of pharmacotherapy have become a mainstay for the management of mood disorders, particularly more severe, chronic, and recurrent forms of depression and most forms of bipolar disorder. This review examines recent developments in the pharmacotherapy of both forms of mood disorder, comparing the newer antidepressants such as the selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors with their predecessors (the monoamine oxidase inhibitors and tricyclic antidepressants) and likewise comparing the older standard for management of bipolar disorder, lithium, with newer classes of medications, such as a selected group of anticonvulsants and the atypical antipsychotics. Although these newer classes of medications have generally improved upon the earlier treatments in terms of better tolerability and safety, there are no universally effective pharmacologic treatments for mood disorders, and careful medical management of these medications is still warranted.

Decreased expression of insulin-like growth factor binding protein 2 in the prefrontal cortex of subjects with bipolar disorder and its regulation by lithium treatment

Insulin-like growth factors (IGFs) regulate cellular proliferation and death, and their bioactivity is controlled by IGF binding proteins (IGFBPs). Since IGFBP-2 is the major brain resident IGFBP, and we have demonstrated lithium-mediated changes in its mRNA and protein levels in neuronal cultures, we examined IGFBP-2 expression in prefrontal cortex postmortem brain tissue from subjects with mood disorders. We found decreased IGFBP-2 expression in bipolar disorder patients compared with controls; this was especially pronounced in subjects not treated with lithium. These results suggest a role for IGFBPs in the etiology and pharmacotherapy of mood disorders.

Pharmacotherapy of Mood Disorders and Treatment Discontinuation

Depression is the most frequent and costly problem in primary care, where most of these patients are seen and treated. In many countries, the public regard antidepressant drugs as 'addictive', partly because of the withdrawal symptoms that can occur when they are discontinued. Indeed, discontinuation (withdrawal) symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin receptor inhibitors (SSRIs). This is important because they are widely regarded as drugs of choice for both depression and the anxiety disorders. But is this true withdrawal or merely rebound? The antidepressant discontinuation syndrome is characterised by the time-locked emergence of new, clearly defined and quantifiable signs and symptoms that ensue on stopping or reducing the dose of an antidepressant. Thereby, it meets the criteria for a withdrawal syndrome. The symptoms are not usually severe or protracted. SSRIs vary in their propensity to be associated with a discontinuation syndrome: paroxetine appears to be the most likely. Patients should be warned of the possibility of developing such a reaction, but reassured that it is usually mild and self limiting. Tapering the dose, if practicable, is worthwhile. In severe cases, temporary reinstatement of the SSRI and slower tapering may be necessary. Escalation of antidepressant dosage, or 'street abuse', is rare with antidepressants. The use of antidepressants is generally beneficial, and efforts should be made to optimise our current use of these drugs as well as encouraging the development of newer, better and innovative compounds. To this end, physicians should educate themselves and the public about discontinuation and withdrawal, so that these clinical features can be put in a realistic context.

Pharmacotherapy of mood disorders in epilepsy: The role of newer psychotropic drugs

Depression in patients with epilepsy (PWE) is a relatively common comorbidity that has a significant negative impact on their quality of life. Therefore, recognition and management of a comorbid depressive disorder is paramount to achieve successful comprehensive treatment in PWE. Depression in epilepsy may mimic primary depressive disorders, but in a significant percentage of depressed PWE, the clinical semiology has an atypical presentation and fails to meed any of the diagnostic criteria established in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Despite the relatively high prevalence of depression in epilepsy and its frequent atypical presentation, there has been only one controlled study (in 1979) to establish the safety and efficacy of antidepressant drugs in PWE. Accordingly, clinicians must rely on data from studies of pharmacotherapy of primary depression. These data are adequate to guide the clinician in the basic principles of pharmacotherapy of depression in PWE. Many questions are yet to be answered, including: 1) are the expectations of symptom remission to pharmacotherapy in PWE different in typical and atypical forms of depression, and do they differ from those of patients with primary depression? and 2) are the doses of antidepressant drugs necessary to yield symptom remission different between PWE and those patients with primary mood disorders?

Treating Mood Disorders During Pregnancy

Mood disorders in pregnancy may have a negative effect on self care and pregnancy outcome that affects the mother directly and the child indirectly. Thus, some women may require pharmacological treatment. Pharmacotherapy of mood disorders during pregnancy implies specific considerations. This paper presents an updated review of available studies on the treatment of mood disorders and present knowledge on teratogenicity, neonatal effects and long-term neurobehavioural effects for the different psychotropic drugs, including treatment with selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), other antidepressants, benzodiazepines, lithium, carbamazepine/valproic acid, lamotrigine and novel antipsychotics. However, the existing knowledge on the use of antidepressants and mood stabilising agents during pregnancy is hampered by a lack of results from randomised controlled trials.SSRIs and TCAs have not been associated with an increased risk of major malformations, but poor neonatal adaptation has been described. Benzodiazepines used in the first trimester have been associated with orofacial clefts. Mood stabilisers such as lithium, carbamazepine and valproic acid (sodium valproate) are associated with an increased risk of fetal malformations. Both benzodiazepines and lithium may cause adaptation problems in the newborn. In utero exposure to novel antipsychotics has not been associated with congenital malformations; however, the data are still limited. The knowledge about long-term neurobehavioural effects in the offspring is still limited for all agents and requires further investigation. Possible adverse effects of fetal exposure must be balanced against the adverse effects of an untreated maternal mood disorder.

Desensitization of 5-HT1AReceptors by 5-HT2AReceptors in Neuroendocrine Neurons in Vivo

An imbalance between serotonin-2A (5-HT2A) and 5-HT1A receptors may underlie several mood disorders. The present studies determined whether 5-HT2A receptors interact with 5-HT1A receptors in the rat hypothalamic paraventricular nucleus (PVN). The sensitivity of the hypothalamic 5-HT1A receptors was measured as oxytocin and adrenocorticotropic hormone (ACTH) responses to the 5-HT1A receptor agonist (+)-8-hydroxy-2-(di-n-propylamino) tetralin hydrobromide [(+)8-OH-DPAT] (40 microg/kg s.c.). The 5-HT(2A/2C) receptor agonist (-)DOI [(-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl] (1 mg/kg s.c.) injected 2 h prior to (+)8-OH-DPAT significantly reduced the oxytocin and ACTH responses to (+)8-OH-DPAT, producing a heterologous desensitization of the 5-HT1A receptors. Microinjection of the 5-HT2A receptor antagonist MDL100,907 [(+)-alpha-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenylethyl)]-4-piperidinemethanol; 0, 10, or 20 nmol, 15 min prior to (-)DOI] into the PVN dose-dependently prevented the desensitization of 5-HT1A receptors induced by the 5-HT2A receptor agonist (-)DOI. Double-label immunocytochemistry revealed a high degree of colocalization of 5-HT1A and 5-HT2A receptors in the oxytocin and corticotropin-releasing factor neurons of the PVN. Thus, activation of 5-HT2A receptors in the PVN may directly induce a heterologous desensitization of 5-HT1A receptors within individual neuroendocrine cells. These findings may provide insight into the long-term adaptation of 5-HT1A receptor signaling after changes in function of 5-HT2A receptors; for example, during pharmacotherapy of mood disorders.

Radioligands for PET and SPECT Imaging of the Central Noradrenergic System

In the central nervous system, the neurotransmitter norepinephrine is involved in normal physiology, neuropsychiatric disorders, and the effects of numerous drugs. Although alterations of the central noradrenergic system are involved in the pathophysiology and pharmacotherapy of mood disorders, the basis and nature of these changes remain unresolved. Positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging agents will be valuable for further elucidating the roles of norepinephrine in health and disease. This review discusses PET and SPECT radioligands that have been developed for the enzymes, receptors, and transporters involved in noradrenergic neurotransmission. Currently, imaging agents that exhibit specific in vivo uptake in the brain have been described for monoamine oxidase A and beta-adrenergic receptors, but have not undergone detailed evaluation or experimental application. Based on the successful development and utilization of in vivo imaging agents for elements of the central dopaminergic and serotoninergic systems, PET and SPECT radioligands are expected to serve as new tools for studying the physiology, pathophysiology, and pharmacology of the central noradrenergic system.

Pharmacotherapy of Mood Disorders and ECT

Pharmacotherapy of Mood Disorders and ECT

Natural history and preventative treatment of recurrent mood disorders.

This chapter focuses on recent developments in our understanding of the etiology, epidemiology, and treatment of recurrent mood disorders. It addresses the changing relationship between endogenous and exogenous factors over time in the etiology of mood episodes. In the area of epidemiology, the chapter presents new information on the prevalence of various subtypes and male/female differences in lifetime risk. Complications of the mood disorders, such as suicide, and important comorbidities, including alcoholism and substance abuse, are discussed. In the area of treatment, the life-long nature of many of the mood disorders is described, as is the consequent role of the primary care physician in their management. The evidence for the efficacy of the depression-specific psychotherapies, cognitive therapy and interpersonal therapy, is reviewed. Current issues in the pharmacotherapy of mood disorders are discussed, including the relative efficacy of the older antidepressants versus the newer selective serotonin reuptake inhibitors (SSRIs) and the treatment of various subtypes of mood disorders, including dysthymia, chronic depression, and atypical depression. Finally, the chapter describes recent advances in the treatment of bipolar disorder.

Recent developments in the pharmacotherapy of mood disorders.

This article reviews recent developments in the pharmacotherapy of mood disorders. Pharmacotherapy is the best studied and most widely validated approach for acute phase treatment and prevention of relapse-recurrence for patients with major depression, dysthymia, and bipolar affective disorder. Antidepressants are also the mainstay of inpatient treatment and, when considered together with electroconvulsive therapy, represent the first line of treatment for the most severe and incapacitating forms of depression. Similarly, pharmacotherapy with mood stabilizers is the first line of treatment for bipolar depression and mania. Despite such efficacy, problems associated with pharmacotherapy include acceptability, tolerability, adherence, incomplete remission, and high rates of recurrence after drug discontinuation. Moreover, a small subset of patients do not respond to multiple medication trials.

Recent developments in the pharmacotherapy of mood disorders.

Recent developments in the pharmacotherapy of mood disorders.