Long established as the preeminent source in its field, the eagerly anticipated fifth edition of Dr Stahl's essential textbook of psychopharmacology is here! With its use of icons and figures that form Dr Stahl's unique 'visual language', the book is the single most readable source of information on disease and drug mechanisms for all students and mental health professionals seeking to understand and utilize current therapeutics, and to anticipate the future for novel medications. Every aspect of the book has been updated, with the clarity of explanation that only Dr Stahl can bring.
Treatments for Mood Disorders: So-Called “Antidepressants” and “Mood Stabilizers”
In this chapter, we will review pharmacological concepts underlying the use of drugs used to treat mood disorders, from depression, to mixed states, to mania. These agents have classically been called “antidepressants” and “mood stabilizers” but this terminology is now considered out of date and confusing since not all drugs classically called “antidepressants” are used to treat all forms of depression – especially not bipolar depression or depression with mixed features. Furthermore, many of the classic so-called “antidepressants” are also used to treat a whole range of disorders from anxiety disorders, to eating disorders, traumatic disorders, obsessive compulsive and impulsive disorders, pain, and beyond. Finally, many of the drugs used for psychosis and discussed extensively in Chapter 5 are used even more commonly to treat depression, unipolar, bipolar, and mixed depression, as well as mania, yet are not generally classed as “antidepressants” although they are certainly “drugs for depression.” To eliminate confusion about how to discuss categories of drugs, throughout this textbook we strive to utilize modern neuroscience-based nomenclature, where drugs are named for their pharmacological mechanism of action and not for their clinical indication.
Thus, drugs discussed in this chapter have “antidepressant action” but are not called “antidepressants.” Other drugs have mood-stabilizing and antimanic action but are not called “mood stabilizers.” What is a “mood stabilizer”? Originally, a mood stabilizer was a drug that treated mania and prevented recurrence of mania, thus “stabilizing” the manic pole of bipolar disorder. Others use this term for a drug that treats depression and recurrence of depression in bipolar disorder thus stabilizing the depressed pole of bipolar disorder. Rather than use the term for stabilizing either mania or depression, here we will use terms to describe and categorize agents that treat bipolar disorder based upon presumed mechanism of therapeutic action.
This chapter will review some of the most extensively prescribed psychotropic agents in psychiatry today, namely those that target neurotransmitter transporters, receptors, and ion channels. The goal of this chapter is to acquaint the reader with current and evolving ideas about how the various drugs used to treat disorders of mood work. We will explain the mechanisms of action of these drugs by building upon general pharmacological concepts introduced in earlier chapters. We will also discuss concepts about how to use these drugs in clinical practice, including strategies for what to do if initial treatments fail and how to rationally combine one drug with another. Finally, we will introduce the reader to several new agents targeting mood disorders, which have recently been approved or are in clinical development.
Our discussion of drugs for the treatment of mood disorders in this chapter is at the conceptual level, and not at the pragmatic level. The reader should consult standard drug handbooks (such as the companion Stahl’s Essential Psychopharmacology: the Prescriber’s Guide) for details of doses, side effects, drug interactions, and other issues relevant to the prescribing of these drugs in clinical practice. Here we will discuss putting together a “portfolio” of two or more mechanisms of action, often requiring more than one drug, as a strategy for patients who have not responded to single pharmacological mechanisms. This treatment strategy for mood disorders is very different than that for schizophrenia, discussed in Chapter 5, where single antipsychotic drugs as treatments are the rule and the expected improvement in symptomatology may be only 20% to 30% reduction of symptoms, with few, if any, patients with schizophrenia becoming truly asymptomatic. By contrast, in mood disorders there is a greater chance to reach a genuine state of sustained and asymptomatic remission and the challenge for those who treat these patients is to help them attain this best outcome whenever possible. That is the reason for learning the mechanisms of action of so many drugs, the complex biological rationale for combining specific sets of drugs, and the practical tactics for tailoring a unique drug treatment portfolio to fit the needs of an individual patient.
For patients who have a major depressive episode, unipolar, bipolar, or mixed, and who receive treatment and improve to the level 50% reduction of symptoms or more, this outcome is called a response (Figure 7-1). This used to be the goal of treatment with drugs for depression: namely, reduce symptoms substantially, and by at least 50%. However, the paradigm for depression treatment has shifted dramatically in recent years so that now the goal is complete remission of symptoms (Figure 7-2), and maintaining that level of improvement so that the patient’s major depressive episode does not relapse shortly after remission, nor does the patient have a recurrent episode in the future (Figure 7-3). Given the known limits to the efficacy of available drugs to treat depression, especially when multiple treatment options are not deployed aggressively and early in the course of this illness, the goal of sustained remission can be difficult to reach. Unfortunately, remission is usually not reached with the first agent chosen to treat depression.