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.
Targets of Treatment: Categories versus Dimensions of Psychopathology
We are much too much inclined in these days to divide people into permanent categories, forgetting that a category only exists for its special purpose and must be forgotten as soon as that purpose is served.
▢ Identify dimensions as well as categories of psychopathology related to mood, thinking, perception, and behavior that may cut across diagnoses and correspond more directly to disordered underlying neural circuitry; at the same time, whenever possible, look for recognizable constellations of symptoms that track together as coherent clinical entities
▢ Recognize form fruste (or, partial) presentations of major clinical syndromes; course over time may help to validate diagnostic constructs and their longitudinal stability
▢ Use knowledge of common comorbidities to corroborate likely diagnostic impressions
▢ Appreciate that transdiagnostic features such as autonomic hyperarousal, distress intolerance, executive dysfunction, and emotional lability may in themselves pose relevant targets for pharmacotherapy
Diagnostic systems such as the DSM have long struggled over whether to organize psychiatric disorders as black-and-white categories defined by operational criteria (where “casehood” is unambiguously either present or absent) versus dimensions of psychopathology (where certain clinical elements are present but insufficient in number or duration to meet minimum criteria that define a particular clinical condition). Clinicians, meanwhile, often tend to identify and treat prominent symptoms, with varying degrees of awareness and concern about their broader context for defining the presence or absence of a distinct syndrome. In this chapter we will examine when pharmacological treatment targets can or should be thought of as unambiguous disease categories as opposed to dimensions of psychopathology that may not always be so clear-cut.
Diagnoses are clusters of signs and symptoms that should form a coherent constellation based on their inter-relationships. Often, no single symptom in itself defines one diagnosis over another, although some cardinal features may point more compellingly toward a particular diagnosis (e.g., suicidality is more diagnostically suggestive of depression than is, say, insomnia). Diagnostic validity becomes especially challenging when no pathognomonic features exist and fundamental symptoms overlap across multiple disorders. Parsimony always favors finding an overarching diagnosis rather than tackling individual symptoms piecemeal, at least when a unifying pathophysiological process can be identified – but it becomes especially difficult to pronounce diagnostic categories as valid when the etiology of most forms of mental illness remains unknown.
Symptom constellations sometimes fall together neatly and nonarbitrarily, as, for example, in eponymous conditions defined by unique symptom conglomerations (e.g., the triad of ptosis + miosis + anhydrosis = Horner’s syndrome; or, ophthalmoplegia + ataxia + confusion = Wernicke’s encephalopathy). Other examples of categorical entities defined by recognizable symptom collections include normal pressure hydrocephalus (the triad of gait abnormalities + urinary incontinence + mental status changes), nephrotic syndrome (defined by proteinuria + hypoalbuminemia + hyperlipidemia + peripheral edema), or multiple sclerosis (characterized by the convergence of weakness, vision changes, paresthesias, and cognitive deficits).
Medical diagnosticians rely on corroborative anatomical or physiological signs and symptoms to affirm a suspected unifying explanation – as when lower extremity edema occurs with rather than without hepatomegaly and pulmonary rales (suggesting congestive heart failure), or when it occurs with rather than without femoral lymphadenopathy (suggesting lymphedema from a possible malignancy). In much the same way, the basis for a categorical diagnosis in psychiatry can often be deduced by amassing clues and corroborative data that ultimately point to an identifiable suspect.
Psychiatric detective work demands clinical curiosity about which signs and symptoms belong together and which ones seem out of place or fail to add up to a coherent whole. Symptom profiles should follow a logical, nonrandom pattern, and should be commensurate with outward functioning or disability. Sometimes, categorical diagnoses emerge with utter clarity when puzzle pieces fit neatly together to tell a coherent story and support a working hypothesis. For examples, see Clinical Vignettes 2.1–2.3.
In a young adult man with auditory hallucinations, the presence of concrete thinking and poor interpersonal relatedness helps to corroborate hypotheses about schizophrenia, while a more affectively related, fairly abstract thinking version of the same patient would less likely arouse such inklings. Rapid resolution of psychotic symptoms might alternatively prompt speculation about psychoactive substance misuse. Concomitant hemiparesis with an aura and blurry vision might instead suggest hemiplegic migraines.
Preoccupations with jumping out of a high-story window of a tall building fit conceptually with depression when accompanied by anhedonia, hopelessness, and vegetative signs, or with obsessive-compulsive disorder when the thoughts are unmistakably intrusive, ego-dystonic, frightening, and contrary to an emotional state of sadness and despair, or with schizophrenia if the intent is to act on or escape from command hallucinations, or with an anxious-insecure attachment style and poor distress tolerance, in the absence of an affective syndrome, following a romantic rejection.
A young adult with complaints of incessant anxiety unrelieved by SSRIs might draw skepticism about the legitimacy of her symptoms when there is also a history of sedative-hypnotic abuse, particularly if the patient claims ardently that only benzodiazepines are helpful, or expresses an intense lack of interest in rigorously exploring pharmacotherapies that are not controlled substances or in considering nonpharmacological treatment options.
DSM psychiatric diagnoses are grounded in phenomenology and make no pretense about knowing the real cause of any mental illness. For all the biological correlates espoused about disease states and their viable remedies – from neurotransmitter systems to aberrant brain circuitry to genetics or endocrinological or inflammatory processes – modern nosology remains atheoretical with respect to the etiology of psychiatric disorders. Biological or laboratory markers sometimes help to affirm suspected diagnoses elsewhere in medicine, although the absence of biomarkers to help validate distinct diagnostic entities is not unique to psychiatry – there are no laboratory or other biological measures to help differentiate migraine from cluster or tension headaches, or Meniere’s disease from vestibular labyrinthitis, or Raynaud’s phenomenon from complex regional pain syndrome. The hunt for biomarkers of mental illness has long been elusive, and tends to ignore the psychological dimensions and context of symptom presentations. Some clinicians and investigators think that until valid biomarkers are identified, the quest for personalized medicine and predictable pharmacodynamics will remain plagued by insurmountable guesswork. We maintain that clinical psychopharmacology need not and should not involve guesswork, and can be pursued using a systematic approach informed by a sufficiently thorough initial clinical assessment.
It is harder to think of diagnostic categories as clearly separable if and when their defining criteria share many overlapping elements such as “psychosis” or “anxiety” or “inattention” or “low motivation” or “mood instability.” Symptom collections that present in unrecognizable or haphazard patterns often defy diagnostic categorization during structured clinical interviews. For practical purposes, such mosaicism often leads clinicians to think about treatment targets as psychopathology dimensions along spectra, rather than trying to spot whether or not a particular category is unambiguously present. And, unlike antibiotics or antineoplastics or antianginal drugs, ameliorative psychotropic drugs do not necessarily correct underlying pathophysiologic processes as much as compensate for them, in much the same way that guaifenesin eases symptoms of a cough but does not fundamentally treat its etiology.
Table 2.1 presents representative examples of overlapping symptoms domains – ranging from sleep/wake cycling disruptions to affective, cognitive, and behavioral phenomena – across varied psychiatric diagnostic categories.
|Symptom/dimension||MDD||Panic disorder||Bipolar disorder||SZ||ADHD||PTSD||SUDs||BPD||NPD||TBI||Dementia|
|Poor impulse control|
|Disorganized form of thinking||✓||✓||✓||✓|
|Nonsuicidal self-injurious behaviors||✓|
|Suicidal thoughts or behaviors||✓||✓||✓||✓||✓||✓|
Abbreviations: MDD = major depressive disorder; ADHD = attention deficit hyperactivity disorder; NPD = narcissistic personality disorder; PTSD = post-traumatic stress disorder; BPD = borderline personality disorder; SUDs = substance use disorders; SZ = schizophrenia; TBI = traumatic brain injury
Psychiatric diagnostic criteria can be fickle and may not always fit together so neatly. They are usually developed by consensus agreement among expert work groups, rather than “discovered” as the natural assemblage of a disease state in the wild. Diagnoses are sometimes voted by committees into or out of existence (e.g., disruptive mood dysregulation disorder and Asperger’s syndrome, respectively). In fairness, though, the defining criteria for some nonpsychiatric medical conditions also can evolve as key elements are thought to assume greater or lesser nosological importance. Examples here would include the American Diabetes Association criteria for Type II diabetes, or the Androgen Excess PCOS Society Criteria for polycystic ovarian syndrome, or the American–European Consensus Sjögren’s Classification Criteria. In both psychiatric and nonpsychiatric medical conditions, consensus-based criteria for a categorical diagnosis often undergo periodic revision as knowledge advances about the relative importance of certain cardinal features. (For example, in 2010 the standardized criteria for Marfan syndrome placed new emphasis on the presence of certain cardiovascular and ophthalmological signs; in schizophrenia, bizarre delusions were at one time considered to hold particular nosologic importance.) Diagnostic criteria are also sometimes revised to reflect changing thresholds for determining when intervention is appropriate (as in the case of revised guidelines for the detection, prevention and management of hypertension by the American College of Cardiologists/American Heart Association).
Psychiatric diagnoses are defined by symptom clusters according to consensus opinion, making their “accuracy” more relative than absolute.
Also similar to nonpsychiatric medical conditions, cross-sectional symptoms comprise only one leg of diagnostic validity, alongside such corroborative features as:age at onset (e.g., first episodes of psychosis or bipolar mania are rare after middle age),longitudinal course (schizophrenia tends more often to involve persistent symptoms and chronic disability; childhood ADHD remits about one-half to two-thirds of the time into adulthood (Kessler et al., 2005a)), andfamily history (which again may reflect symptom clusters (such as suicidal behavior, impulsivity, or social aversion) more accurately than syndromes being categorically present or absent).
Psychiatric diagnostic categories tend to be reliable (meaning observers can reasonably agree on their presence or absence) more than valid (meaning they accurately discriminate one genuine underlying process from another). Even when there exists a sine qua non individual symptom that defines a condition, constellations with other symptoms often remain important. When does inattention denote ADHD, or when is it merely the symptom of a broader construct? Like the showy lead singer of a band, or the soloist in a choral ensemble, one highly prominent symptom could easily unduly overshadow other aspects of a constellation. Here one runs the risk of overgeneralizing the importance of a particular clinical feature, then jumping the gun pharmacologically, and neglecting altogether the concept of differential diagnosis. Examples include presumptions such as:
self-injury or self-mutilation behavior equates to borderline personality disorder
mood swings equate to bipolar disorder
inattention or poor concentration means ADHD
bizarre delusions or first-rank symptoms equate to schizophrenia
a history of trauma automatically equates to post-traumatic stress disorder (PTSD)
A single symptom, however prominent, does not in itself equate to a psychiatric diagnosis.