This chapter focuses on women's mental health issues as they relate to depression. Specifically, women are at more risk than men for developing depression throughout their lifetimes, especially during their childbearing years. The incidence of depression in women rises during puberty. High-risk periods for onset or recurrence of a major depressive episode include the postpartum period and the perimenopausal transition to menopause. This chapter discusses how fluctuations of estrogen levels may be linked to the onset or recurrence of a major depressive episode in a woman, and provides some tips for how to manage depression in women, including evolving findings about treatment of vasomotor symptoms associated with the onset or recurrence of depression during perimenopause.

This chapter reviews the antidepressant drugs that are combined norepinephrine dopamine reuptake inhibitors (NDRIs) and selective norepinephrine reuptake inhibitors (NRIs), and that are currently available to clinicians. NDRIs are considered first-line treatment, and NRIs are often second-line. Each drug in these classes is reviewed. The aim of this chapter is to familiarize the reader with these options for treating depression.

SSRI: selective serotonin reuptake inhibitors. NDRI: norepinephrine dopamine reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. SDA: serotonin dopamine antagonists. α 2 antagonist: alpha 2 antagonists. NRI: selective norepinephrine reuptake inhibitors. TCA: tricyclic antidepressants. SARI: serotonin 2A antagonist/reuptake inhibitors. MAOI: monoamine oxidase inhibitors. 5HT1A: serotonin 1A partial agonists. BZ: benzodiazepines. DPA: dopamine partial agonists. MTHF: L-5-methyl-tetrahydrofolate. T3/T4: thyroid hormone. ECT: electroconvulsive therapy. IPT: interper-sonal therapy. VNS: vagus nerve stimulation.

Bupropion may be useful in treating nicotine addiction due to its ability to occupy DATs in the striatum and nucleus accumbens, mitigating cravings but not becoming abusable itself. Bupropion was originally marketed in the United States only, and in an immediate-release formulation. Recent formulations have been developed in twice-daily (bupropion SR) and once-daily doses (bupropion XR). These advances not only provide convenience but are also beneficial in reducing the risk of seizures at peak plasma drug levels associated with the original formulation. Bupropion is generally a stimulating agent, and does not appear to cause sexual dysfunction that may be associated with use of other antidepressants. Bupropion has been very useful for patients who experience reduced positive affect, or the “dopamine-deficiency syndrome” (see Fig. 1.35). Oftentimes, augmentation with bupropion to an existing SSRI or SNRI can be useful for patients who have not responded to previous serotonergic-focused treatment.

CME credit has expired for this activity (2/28/15). You are welcome and encouraged to complete the activity and posttest for your personal enrichment, but will not be able to receive credit nor print a certificate for this activity.

(Original CME Information)

Overview

This book aims to visually explain the concepts behind the neurobiology of depression, as well as the current and novel treatment options available to clinicians to treat depression. The book is divided into eight chapters for ease of reading and referencing. Chapter 1 focuses on the neurobiology behind depression, with an emphasis on the neurotransmitters involved in the experience of depressive symptomatology: serotonin, norepinephrine and dopamine. Chapter 2 begins the introduction of antidepressant drug classes, with an overview and in-depth explanation of each drug in the SSRI and SNRI classes. Chapter 3 covers NDRIs and NRIs; Chapter 4 features SNDIs and SARIs; Chapter 5 examines the older generation of antide-pressants— MAOIs and TCAs; and Chapter 6 introduces novel treatment options for managing depression. Chapter 7 focuses on depression in women, emphasizing the role that estrogen plays in the experience of depressive symptomatology. Chapter 8 reviews the pharmacokinetics of antidepressants, and introduces algorithms commonly used to treat depression. The visual component of this book is designed to allow the reader to easily grasp complex concepts.

Target Audience

This activity has been developed for prescribers specializing in psychiatry. There are no prerequisites. All other health care providers interested in psychopharmacology, are welcome for advanced study.

Statement of Need

• • The following unmet needs and professional practice gaps regarding antidepressants were revealed following a critical analysis of activity feedback, expert faculty assessment, literature review, and through new medical knowledge:

• • Not all antidepressants are efficacious in all patients; thus, it is important for mental health professionals to be aware of alternative options.

• • Full remission and recovery is still the gold standard for depression, yet only 50% of responders actually achieve remission.

• • The most common residual symptoms of treatments for depression are insomnia, hypersomnia and physical fatigue/pain, and executive dysfunction.

To help address clinician performance deficits with respect to treating depression, quality improvement efforts need to provide education that will increase understanding of the neurobiology of psychiatric disease states and the pharmacology of available, new, and in-development medications.

Several emerging treatment options for depression have shown promise, especially for patients resistant to treatment with first-line drugs. Described in this chapter are a variety of options that may assist in treating depression, whether as a monotherapy or in combination with another drug of choice. The concept of trimonoamine modulators (TMMs) is introduced to explain the actions of many agents used to augment anti-depressants including lithium, thyroid, and L-methylfolate. Estrogen as a TMM is explained in the following chapter. Various forms of brain stimulation/neuromodulation are also illustrated here, from vagus nerve stimulation (VNS) to transcranial magnetic stimulation (TMS) to deep brain stimulation (DBS). A few new therapeutic approaches to the treatment of depression are also included at the end of the chapter.

This chapter reviews the actions of antidepressant drugs that work as alpha 2 antagonists (i.e., mirtazapine) or as serotonin antagonist/reuptake inhibitors (SARIs) (i.e., trazodone and nefazodone). The focus is on the unique characteristics of alpha 2 antagonism and SARIs, both of which are second-line treatment options. The aim is to familiarize the reader with these various options for treating depression.

SSRI: selective serotonin reuptake inhibitors. NDRI: norepinephrine dopamine reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. SDA: serotonin dopamine antagonists. α 2 antagonist: alpha 2 antagonists. NRI: selective norepinephrine reuptake inhibitors. TCA: tricyclic antidepressants. SARI: serotonin 2A antagonist/reuptake inhibitors. MAOI: monoamine oxidase inhibitors. 5HT1A: serotonin 1A partial agonists. BZ: benzodiazepines. DPA: dopamine partial agonists. MTHF: L-5-methyl-tetrahydrofolate. T3/T4: thyroid hormone. ECT: electroconvulsive therapy. IPT: interper-sonal therapy. VNS: vagus nerve stimulation.

Mirtazapine's antagonist actions at 5HT2A and 2C receptors also results in increased release of dopamine and norepinephrine, and these 5HT2A and 5HT2C antagonist actions may also provide useful anxiolytic and antidepressant as well as sleep-restoring properties. In addition, mirtazapine is able to increase serotonin release without causing sexual dysfunction.

Due to its 5HT2A and 5HT2C antagonist properties, and thus its ability to disinhibit both NE and DA release (see Figs. 1.32 and 1.33), mirtazapine is further classified as a norepinephrine and dopamine disinhibitor (NDDI). 5HT3 antagonist action may reduce nausea, with H1 action potentially relieving insomnia and improving anxiety, but causing weight gain. So, this complex molecule is an NDDI (due to 5HT2A and 5HT2C antagonism), an SNDI (due to alpha 2 antagonism) plus a 5HT3 and H1 antagonist!

Pharmacokinetics of antidepressants must be considered when choosing and combining treatments for patients. Information on drug interactions is constantly being updated. This chapter reviews the basic principles of antidepressant pharmacokinetics, but specifics are best found in up-to-date reference sources on prescribing.

Once treatment options have been investigated, algorithms to treat depression may help the clinician in deciding the best treatment choice on a per-case basis. Current algorithms that may be utilized in the treatment of depression can be evidence-based, cost-based or symptom-based. Whereas evidence- and cost-based algorithms may be more beneficial to healthcare plans in terms of financial issues, patients often benefit most from a symptom-based approach. This may require some trial and error, but once the correct treatment option is chosen, patients may experience complete remission of depressive symptoms. Whatever approach is taken, the goal of treatment of depression is remission. Here, we emphasize the symptom-based approach to selecting and combining antidepressants, particularly for difficult cases.

MDD: major depressive disorder. NDRI: norepinephrine and dopamine reuptake inhibitors. NRI: norepinephrine reuptake inhibitors. SSRI: selective serotonin reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. SARI: serotonin antagonist/reuptake inhibitors. MAOI: monoamine oxidase inhibitors. 5HT: serotonin. NE: norepinephrine. DA: dopamine.

SSRI: selective serotonin reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. NDRI: norepinephrine and dopamine reuptake inhibitors. 5HT1A: serotonin 1A agonists. T3/T4: thyroid hormone.

SSRI: selective serotonin reuptake inhibitors. NDRI: norepinephrine and dopamine reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. ECT: electroconvulsive therapy. IPT: interpersonal therapy. VNS: vagus nerve stimulation. NRI: norepinephrine reuptake inhibitors. TCA: tricyclic antidepressants. SARI: serotonin 2A antagonist/reuptake inhibitors. MAOI: monoamine oxidase inhibitors.

SSRI: selective serotonin reuptake inhibitors. NDRI: norepinephrine and dopamine reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. DPA: dopamine partial agonists. MTHF: L-5-methyl-tetrahydrofolate.

Depression can affect every aspect of life. A patient undergoing a major depressive episode who receives treatment with any antidepressant will often experience symptomatic improvement. However, oftentimes treatment does not reach the goal of remission (complete cessation of all symptoms of depression) until several different pharmacotherapies have been utilized, possibly in combination. Understanding the neurobiology underlying depressive symptomatology may allow clinicians the opportunity to treat the symptoms specifically, based upon brain mechanisms and the interplay among genes, circuits and symptoms. This chapter focuses on the neurobiology of depression, and offers a review of the three monoamines hypothetically linked not only to the symptoms of a major depressive episode, but also to the treatment of those symptoms.

This chapter reviews some of the most commonly used first-line antidepressant drug options, the selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). For patients who do not completely remit on an SSRI or SNRI, oftentimes augmentation and/or combinations are introduced or the patient is switched to a second-line treatment. This concept is developed in further detail in later chapters. Here, each of the six drugs in the SSRI class and each of the four drugs in the SNRI class is reviewed.

• • Three neurotransmitters involved in the regulation of depressive symptomatology were discussed: serotonin, norepinephrine and dopamine

• • Circuits include pathways extensively traveled by 5HT, NE and DA

• • Various genes are risk factors for depression

• • Depression can often be treatment-resistant, resulting in the need for several different drug combinations prior to achieving response and full remission

• • There are currently many classes of antidepressants available, with SSRIs, SNRIs and NDRIs most often considered first-line treatment options

• • Augmentation of these first-line treatments can be selected by using a symptom-based strategy; that is, choose treatments most likely to reduce each individual patient's specific symptoms based upon the underlying neurobiological ratio-nale for these symptoms

• • Several new treatments for depression are on the horizon

This chapter reviews the classical antidepressants known as monoamine oxidase inhibitors (MAOIs) and tricyclic antidepressants (TCAs). The focus here is on mechanisms of action of these particular classes. The aim of this chapter is to familiarize the reader with these “old-fashioned” but quite powerful options for treating depression.

SSRI: selective serotonin reuptake inhibitors. NDRI: norepinephrine dopamine reuptake inhibitors. SNRI: serotonin norepinephrine reuptake inhibitors. SDA: serotonin dopamine antagonists. α 2 antagonist: alpha 2 antagonists. NRI: selective norepinephrine reuptake inhibitors. TCA: tricyclic antidepressants. SARI: serotonin 2A antagonist/reuptake inhibitors. MAOI: monoamine oxidase inhibitors. 5HT1A: serotonin 1A partial agonists. BZ: benzodiazepines. DPA: dopamine partial agonists. MTHF: L-5-methyl-tetrahydrofolate. T3/T4: thyroid hormone. ECT: electroconvulsive therapy. IPT: interpersonal therapy. VNS: vagus nerve stimulation.