Despite the lack of guidance available for practitioners, extensive polypharmacy has become the primary method of treating patients with severe and chronic mood, anxiety, psychotic or behavioral disorders. This ground-breaking new book provides an overview of psychopharmacology knowledge and decision-making strategies, integrating findings from evidence-based trials with real-world clinical presentations. It adopts the approach and mind-set of a clinical investigator and reveals how prescribers can practice 'bespoke psychopharmacology', tailoring care to the individualized needs of patients.
Disordered Mood and Affect
The world breaks everyone and afterward many are strong at the broken places.
▢ Understand how dimensions of mood disorders, such as polarity, psychosis, chronicity, recurrence, and comorbidites are moderators of pharmacotherapy outcome
▢ Know the evidence base for use of antidepressants in adjustment disorders
▢ Describe the relative efficacy of monoaminergic antidepressants for major depressive episodes
▢ Understand the interplay between medication dose, duration, illness chronicity, and speed of pharmacodynamic onset
▢ Know plausible rationales for switching versus augmenting pharmacotherapies for mood disorders after an initial inadequate response
▢ Understand the evidence base and dosing strategies for pharmacotherapies in treatment-resistant depression
▢ Describe evidence-based treatments for depression with comorbid anxiety and other psychiatric conditions
▢ Identify evidence-based pharmacotherapies for depression relapse prevention after ECT
▢ Recognize clinical candidacy criteria for using antidepressants, lithium, and particular anticonvulsants, SGAs or other psychotropic agents across phases of bipolar disorder
Younger readers may not appreciate that prior to DSM-IV, the phenomena that we today call “mood disorders” were identified more precisely as affective disorders, denoting a fundamental distinction between disturbances of mood (the subjective experience of emotion) and affect (the objective behavioral expression of mood). Given that problems with “mood” are ubiquitous throughout virtually all aspects of psychopathology, links between the signs and symptoms of “mood problems” are critical both to nosological classification and to identifying targets of pharmacotherapy interventions. Features associated with affective disorders encompass problems with energy, the sleep–wake cycle, thinking and perception, impulse control, cognition (e.g., attentional processing, problem-solving), motivation/arousal, and eating behaviors, among others.
In this chapter, we present information about the treatment of mood/affective disorders as a broad overarching category, with subdistinctions (such as polarity) highlighted as clinical descriptors, rather than as fundamentally different illnesses. This may trouble some readers. Yet, one could slice the affective pie innumerable ways. Box 13.1 summarizes at least 20. Arguably, each of these dimensions could constitute its own illness, as opposed to instead representing (in our view) distinct moderators of treatment outcome. Additionally, one could classify affective disorders based on specific drug responsivity (analogous to how one classifies some infectious diseases based on their being antibiotic-responsive or -resistant), or perhaps some day, based on biomarker corroborators (remember DST nonsuppressive depression? If not, read on). In keeping with the spirit of practical psychopharmacology, and fostering a more dimensional than categorical approach to diagnosis and treatment, we will focus on dimensions of affective disorders rather than attempt to tackle 20 or more nosologically “unique” categories of mood problems.
|– Polarity (uni- versus bi-)||– Early versus late onset|
|– Persistent (dysthymic/chronic)||– Late-life versus younger adult versus pediatric|
|– Highly recurrent versus nonrecurrent||– Seasonal versus nonseasonal|
|– Psychotic versus nonpsychotic (and therein: mood congruent versus incongruent)||– Treatment-resistant versus nonresistant|
|– Endogenous versus reactive (formerly “neurotic”)||– Medically comorbidly ill|
|– Catatonic||– Primary versus secondary to other medical conditions/substance use|
|– Typical versus atypical||– Pregnant or postpartum|
|– Anxious versus nonanxious||– Inflammatory versus noninflammatory|
|– Agitated versus anergic|
|– Noradrenergic symptom cluster|
|– High versus low severity|
Some of the terminology noted in Box 13.1 has become antiquated in modern parlance (e.g., DSM-5 subsumes “dysthymic disorder” with chronic major depression under the broad heading of “persistent depressive disorders,” and the terms “endogenous” and “neurotic” are no longer recognized). Nevertheless, many clinicians still draw on at least some of the concepts behind these elements when they formulate a clinical presentation and consider pharmacotherapy decisions. As discussed in Chapter 5, most real-world patients manifest various combinations of features such as those listed in Box 13.1, generating a unique clinical profile for every patient as an individual. Certain symptom clusters – such as anhedonia, indecisiveness, and diminished activity – may hold particular negative prognostic importance above and beyond moderators such as baseline severity (Uher et al., 2012). And even affective polarity – considered by some as a sacrosanct dichotomy in mood disorders – really represents just one of many moderating factors that influence course and outcome. To classify someone’s ailment based solely on one moderating characteristic to the exclusion of others oversimplifies the complexity of mood disorders and can unwittingly set the stage for poor outcome to an ostensibly appropriate treatment for a given disorder.
The American Psychiatric Association Practice Guideline for the Treatment of Major Depressive Disorder, 3rd Edition (2010) states that “An antidepressant medication is recommended as an initial treatment choice for patients with mild to moderate major depressive disorder and definitely should be provided for those with severe major depressive disorder unless ECT is planned.” More specific, additional relevant considerations should rightfully include high severity, melancholic features, suicidality, psychosis, functional impairment, and chronicity. It is worthwhile to assess a patient’s attitudes and expectations about what medications can and cannot do, and to gauge outcomes from past psychotherapy or other nonprescription interventions (e.g., exercise, light therapy, nutraceuticals). Equally important is forecasting the likelihood of medication responsivity: Is there an a priori reason to think someone might not benefit from a traditional monoaminergic antidepressant? A history of complete nonresponses to numerous prior adequate antidepressant trials certainly does not contraindicate more antidepressant trials, but demands considerable reflection, lest one continue to do the same thing over and over again and expect different results (consider, for example, the ever-increasing likelihood of remission after multiple iterative antidepressant trials, as illustrated in Box 13.6, below). Is there an untreated medical, psychiatric or substance-use comorbidity that requires hierarchically more immediate attention? Or, does a depressive episode entail mixed (manic or hypomanic) features, which could be worsened by traditional antidepressants (Frye et al., 2009)? Has psychosis been missed? Has treatment adherence been poor?
Consider also whether another psychiatric condition may be present for which “depression” may be a chief complaint but syndromal criteria for an MDE are absent, and the presenting symptoms could be mimicking depression (e.g., negative symptoms of schizophrenia, abstinence or withdrawal symptoms of alcohol or an illicit substance, mania which the patient incorrectly identifies as depression, frank psychosis (for which an antipsychotic is likely a more core treatment than an antidepressant) or an adjustment disorder with depressed mood for which syndromal criteria of a major depression are absent.
Clinicians generally presume that adjustment disorders with depressed mood (historically also referred to as “situational” depressions) are self-limited psychological phenomena that either do not require or otherwise do not empirically benefit from antidepressant pharmacotherapy. (At the same time, some experts think that adjustment disorders may be form fruste presentations that confer a higher risk for eventual development of a full depressive syndrome.) From an evidence-based standpoint, this is actually a very interesting and largely unstudied question with only limited empirical data. Preliminary, small open trials have examined bereavement (normal grief) in the absence of a syndromal MDE and suggested possible benefit from bupropion (150–300 mg/day for eight weeks), showing improvement from baseline depression symptom severity (HAM-D scores) as well as grief intensity ratings (Zisook et al., 2001). More recently, an RCT of a structured psychotherapy (complicated grief treatment (CGT)) plus citalopram significantly improved associated subthreshold depressive symptoms more than CGT alone, but overall outcome was no better with CGT + citalopram than with CGT alone (Shear et al., 2016). Patients who present solely with depressed mood in the context of a devastating interpersonal or other adverse life event that might also evolve into an MDE should be screened for a personal and family history of significant affective illness, and should be monitored for clinical worsening and the potential future role for pharmacotherapy in the event that psychotherapy and/or the natural course of time alone fails to avert progression and worsening of the condition.