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.
Managing Major Adverse Drug Effects: When to Avoid, Switch, or Treat Through
The remedy is worse than the disease.
▢ Understand ways to establish likely cause-and-effect relationships for suspected adverse drug effects
▢ Understand the phenomenology of the nocebo effect
▢ Differentiate relative degrees of binding affinity for psychotropic drugs at key receptor sites associated with clinically significant adverse drug effects
▢ Recognize comparative psychotropic and other risk factors for QTc prolongation
▢ Identify viable pharmacological antidote strategies for managing common nonhazardous adverse psychotropic drug effects
We hope that things have changed for the better since the time of Sir Francis Bacon’s seventeenth-century appraisal of medical treatment risks and benefits. Drugs themselves may not know the differences between the beneficial versus adverse effects they may exert, but prescribers should. All substances, even placebos, can cause negative effects in the minds and bodies of those who consume them, depending on expectations (e.g., past experiences, perceptions of help versus harm), underlying psychopathology (e.g., anxiety, somatization, paranoia), psychological dimensions (e.g., an external locus of control, suggestibility) as well as pharmacokinetics (e.g., delayed metabolic clearance) and, last but not least, pharmacodynamics. Paradoxical drug reactions (such as worsening of psychosis after starting an antidopaminergic drug, or intensified suicidal thoughts or urges after beginning an antidepressant) pose especially challenging dilemmas, as clinicians must try to determine when, faced with a clinical effect opposite to the one expected, there exists a truly iatrogenic effect versus the natural course of illness with mere lack of efficacy (at least thus far) of the chosen intended remedy.
In establishing likely causal connections between a potential medication and a suspected adverse effect, it can be useful to consider the items in Box 10.1.
Adverse effects due to placebos are termed nocebo effects. These most often (>10% of patients) include dizziness, headache, nausea, diarrhea, sedation, insomnia, anorexia, nervousness, and anxiety.
Is there a plausible (versus contradictory) mechanism (e.g., anticholinergic drugs are unlikely to cause sialorrhea) and time course (e.g., drug rashes are unlikely to occur years after having begun a drug)
How far in time did the suspected adverse effect arise relative to the last change made in a drug regimen?
How confident is the clinician that the suspected adverse effect is not simply a manifestation of the underlying psychiatric condition being treated (e.g., worsening suicidal thoughts in a depressed patient, or nonspecific symptoms in a patient with somatic symptom disorder)
Is the suspected adverse effect likely common and transient (e.g., headache or nausea upon starting an SSRI or SNRI) and prone to resolve spontaneously?
Is the suspected adverse effect annoying (e.g., yawning from SSRIs, mild weight gain, benign rashes), potentially hazardous (e.g., metabolic dysregulation, impaired balance) or serious and potentially life-threatening (e.g., Stevens–Johnson syndrome, anaphylaxis)?
Particularly given the varied cognitive, emotional, and perceptual disruptions to information processing that are inherent to psychiatric (as compared to most nonpsychiatric) disorders, care must be taken to evaluate complaints of adverse effects beyond their superficial face value. In RCTs of depression, reported adverse drug effects occur in about two-thirds of subjects taking placebo, and 5% may drop out prematurely specifically due to perceived adverse effects during placebo treatment (Dodd et al., 2015). Termed nocebo effects by Barsky and colleagues (2002), they may be more likely to arise in patients with high levels of neuroticism, phobic-obsessive traits, suggestibility, alexithymia, and excessive or elaborate expectations about treatment outcomes (Goldberg and Ernst, 2019).
A comprehensive review and discussion of all adverse effects associated with psychotropic drugs is beyond the scope of this chapter, although for a more detailed discussion the reader is invited to see Goldberg and Ernst (2019). In the current chapter, our focus will be directed more toward a concise summary of major adverse effects and the psychotropic drugs likely to cause them, along with practical recommendations about their assessment and management.
Countless obscure complaints are sometimes attributed to medications as side effects. Rare possible side effects can occur with any drug, but cause-and-effect relationships may be hard to infer. In such instances it can be useful to tell patients (or colleagues) that the chance of a certain drug causing a particular side effect is no greater than is the case with a placebo.
Acne can result from (or become exacerbated by) use of lithium, possibly because of increased neutrophil chemotaxis, stimulation of lysosomal enzyme release, and induced follicular hyperkeratosis (Yeung and Chan, 2004). Topical benzoyl peroxide, retinoids (e.g., retinoic acid cream or gel), and antibiotics (clindamycin, erythromycin, tetracycline) remain the usual preferred management strategies. Notably, acne caused or exacerbated by lithium can be notoriously difficult to treat and tends to respond more poorly to traditional acne regimens than in the absence of lithium. Spironolactone, which is often prescribed for women with adult acne and hirsutism because of its putative antiandrogenic effects at the site of sebaceous glands, can increase lithium levels and is sometimes advised with careful monitoring of lithium levels.