Table 1.

Identifying ADRs, withdrawal symptoms, and relapse.

Appearance of symptom in daily drug and symptom diary over at least several days	Potential interpretation	Aids to refine identification or resolution
Regularly, every day (single drug)	Adverse drug reaction	• Often more intense after drug is ingested138 • Review pharmacokinetics of individual drugs (note active metabolites)139,144 • Daily lifestyle habit (e.g., caffeine, vitamins) • Taper offending drug to avoid withdrawal symptoms
Regularly, every day (polypharmacy)	Drug–drug interaction	• Drug interaction report133 • Review pharmacokinetics of individual drugs (e.g., peak plasma, active metabolites) • Gradually separate dosing schedule of drugs taken simultaneously, monitor to see if timing of symptom moves with timing of drug dosing145 • Taper offending drug to avoid withdrawal symptoms
Regularly, every day (all psychotropics)	Paradoxical reaction	• Indicates dosage is too high135,146 • Usually activation shortly after drug ingestion138 • Often sleeplessness, anxiety, panic, akathisia136 • Gradually reduce dosage of offending drug to avoid withdrawal symptoms147
Regularly, every day (hypnotics or short-acting drugs)	Rebound, breakthrough, or interdose withdrawal	• Occurs when drug action is wearing off136 • Withdrawal symptoms from hypnotics are often sleeplessness, anxiety, panic • Distribute dosing schedule to resolve symptoms (or convert to long half-life drug)109,140,148 • Indicates physiological dependency requiring gradual taper115,136 • Gradually taper sleep drugs to avoid withdrawal symptoms (e.g. rebound insomnia)136
Sporadic, usually in waves, unrelated to drug cycle	Withdrawal symptom	• Check for irregular dosing149 • May occur after drug switch78 • If recent reduction in dosage, slight updose may resolve72,73 • Check for menstrual cycle, when withdrawal symptoms may worsen150
Sporadic or constant, but persists for more than 6 weeks after discontinuation27,32	PAWS or PWS	• Low-dose reinstatement may resolve (see above) • Caution: potential withdrawal-induced hyper-reactivity to additional psychotropics (kindling)
Constant, but new symptom, started during drug treatment	Adverse drug effect or withdrawal symptom27	• More intense shortly after taking the drug, less after passage of half-life – dosage may be too high (gradually reduce dosage to avoid withdrawal symptoms)147 • Adverse drug effect can be akathisia, emotional anesthesia151 • Check for irregular dosing, can cause withdrawal symptoms149 • If recent reduction in dosage, slight updose may resolve72,73 • Check for menstrual cycle150
Constant, started before drug treatment	Ineffective drug treatment or relapse	• If drug taken more than a month, gradually reduce dosage to avoid withdrawal symptoms134 • Rule out adverse reactions, withdrawal symptoms, and PWS27,32,78

ADR, adverse drug reaction; PAWS, post-acute withdrawal syndrome; PWS, protracted withdrawal syndrome.