Mineral supplements (e.g., zinc and selenium), oral biotin, or topical minoxidil may be worth attempting for the treatment of alopecia, but scalp hair loss attributable to psychotropic medications may be difficult if not impossible to counteract except through cessation of the suspected causal agent.
Diffuse scalp hair loss (telogen effluvium) has been reported in conjunction with several psychotropic medications, perhaps most notably with divalproex (incidence from 12% to 24%), lithium (incidence up to 10%), and carbamazepine (incidence up to 6%) (McKinney et al. 1996), and more rarely with fluoxetine, sertraline, venlafaxine, fluvoxamine, topiramate, amphetamine, methylphenidate, dopamine agonists, perphenazine, TCAs, olanzapine, risperidone, and mirtazapine. Reports also exist of hair loss occurring with one SSRI but not another in the same patient. A World Health Organization database for international drug monitoring also identified a total of 337 cases of suspected lamotrigine-associated alopecia through April 1, 2009, occurring most often in women age <40 years and often resolving after drug cessation (Tengstrand et al. 2010).
Hair loss has been reported as a relatively rare adverse effect of a number of nonpsychotropic medications, including isotretinoin, allopurinol, androgens (testosterone formulations), anticoagulants, β-blockers, calcium channel blockers, colchicine, efavirenz, ergot alkaloids (migraine prophylaxis), NSAIDs, oral contraceptives, propylthiouracil, and ribavirin. A number of medical causes of alopecia warrant investigation before assuming that hair loss is an adverse effect of a suspected psychotropic agent. These include hypothyroidism, autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis, vitiligo, and ulcerative colitis. Chemical damage caused by permanent curls or other caustic cosmetic products may cause hair loss in some individuals. Patchy areas of hair loss or hair loss in nonscalp areas might prompt clinicians to consider the possible presence of trichotillomania. Sudden physical or emotional stresses can be associated with hair loss over a period of weeks to months.
Alopecia from divalproex has been suggested to arise from interference with absorption of dietary zinc and selenium, for which supplementation (25–50 mg/day of zinc and 100–200 μg/day of selenium) is sometimes recommended. Case reports also suggest the possible efficacy of oral biotin 10,000 μg/day. However, in clinical practice, the efficacy of this strategy may not be robust. Cessation of divalproex generally halts the problem. The extended-release formulation of divalproex has been suggested by some to minimize the potential for alopecia (as reflected in a 7% incidence of alopecia during trials of Depakote ER for migraine headache, as compared with 13%–24% with Depakote DR for complex partial seizures), possibly via more distal absorption of the drug with lesser likelihood to interfere with gastrointestinal absorption of dietary minerals. Dosage reductions generally have not been shown to reverse drug-associated alopecia, although comparative studies of high- versus low-dose divalproex for complex partial seizures demonstrated more frequent alopecia among high-dose (24%) than low-dose (13%) recipients. Other clinicians advocate the use of topical minoxidil as a potential remedy; this option is likely safe, although it has not been systematically studied for this purpose.
For sweating induced by SSRIs, SNRIs, or TCAs, clonidine 0.1 mg/day or terazosin 1–2 mg/day may be more effective than anticholinergic remedies such as benztropine 1 mg/day. Preliminary data also support the use of oxybutynin 5 mg qd–tid.
Excessive sweating (hyperhidrosis) occurs in up to 20% of individuals who take antidepressants, both as a daytime phenomenon or as night sweats, and may be dose related. It does not appear to dissipate during prolonged treatment but does remit when the causal antidepressant is stopped. Mechanisms thought to account for this phenomenon include dysregulation of cholinergically innervated sweat glands and dysregulation of the hypothalamic thermoregulatory center, mediated by prodopaminergic tone with reciprocal downregulation of serotonergic tone. Consequently, the most frequently employed strategies to counteract antidepressant-induced hyperhidrosis include anticholinergic agents, such as benztropine dosed at 1 mg/day (although its apparent benefit may be transient), and antiadrenergic agents, such as the α2-adrenergic agonist clonidine (0.1 mg/day) or the α1-adrenergic antagonist terazosin (1–2 mg/day), with visible efficacy within 3–4 weeks. The likelihood of sedation from either of the latter two agents would favor their use in a single nighttime dose. Other anticholinergic drugs that may be of value to counteract iatrogenic hyperhidrosis include glycopyrrolate 1 mg qd or bid or oxybutynin 5–10 mg qd–tid. Case reports also identify benefit with adjunctive mirtazapine (up to 60 mg/day) or the serotonin-blocking drug cyproheptadine 4 mg qd or bid, without reversing antidepressant efficacy.
Adjunctive aripiprazole 10 mg/day, but not ziprasidone, has been reported to alleviate daytime hyperhidrosis caused by fluoxetine or duloxetine, with a mechanism hypothesized to involve both its serotonin type 2A (5-HT2A) antagonism and its dopaminergic partial agonism as modulating the hypothalamic thermoregulatory center (Lu et al. 2008).
Clinicians should counsel patients about the potential for sun exposure to cause burnlike or hyperpigmentation reactions to antipsychotics (mainly FGAs) and less often to TCAs. Adequate prophylactic use of sunscreen is essential when patients are outdoors during warmer months. Photosensitivity reactions should be treated by use of conservative interventions (e.g., aloe lotions) and avoidance of further sun exposure until the resolution of signs and symptoms.
Phototoxic (i.e., nonimmune-mediated) sunburn-like reactions have long been recognized after sun exposure in patients taking FGAs (particularly chlorpromazine, occurring in up to 25% of patients, typically with dosages ≥400 mg/day) (Harth and Rapoport 1996). Case reports of phototoxic reactions also exist with some SGAs, including risperidone and clozapine. Photosensitivity-induced hyperpigmentation has been described as a relatively rare phenomenon in patients taking TCAs.
Adequate prevention of phototoxic reactions involves counseling patients who take antipsychotic medications to minimize sun exposure and make use of full skin protection from ultraviolet A and B (UVA, UVB) wavelengths. Typical treatment for photosensitivity reactions should include avoidance of further sun exposure and application of cool, wet dressings and emollient (e.g., aloe-based) lotions. Topical corticosteroids, NSAIDs, and oral antipruritic (e.g., antihistamine) agents are also sometimes helpful. Oral corticosteroids are more rarely indicated in the setting of more severe or persistent phototoxic reactions that do not remit with more conservative management.
Evaluation of acute pruritus should include a general medical assessment with awareness of the most common dermatological and systemic conditions other than drug rashes that may be causal.
Generalized pruritus in the absence of a visible skin rash can occur with a variety of psychotropic agents, although the differential diagnosis of pruritus with respect to underlying medical etiologies is considerable. The sheer presence or absence of pruritus conveys little information about the nature of a suspected drug rash, other than that certain distinct types of rashes are usually pruritic (notably, atopic or allergic contact dermatitis, psoriasis, and seborrheic dermatitis); whether or not a rash is pruritic does not help to determine if it is likely drug related. Pruritic drug reactions may be allergic and usually are morbilliform or urticarial (see definitions in Table 8–1).
Transient white discoloration of a skin lesion that occurs with pressure
Fluid-filled blisters greater than 5 mm in diameter
Lesions that intermingle, often with ill-defined borders
Exanthematous (synonymous with maculopapular)
Meaning “eruptive”; skin eruptions or rashes
Exfoliative (also desquamative)
Peeling or shedding of skin in flakes or scales
Skin that has become thickened and leatherlike
Maculopapular (synonymous with exanthematous)
Macular: flat and circumscribed (typically <1 cm in diameter); papular: solid and elevated above the surrounding skin
Rash that is measles-like in appearance
Visible collections of pus
Rash that rises above skin level
Rash that indicates an inflammatory process
Inflamed areas with loss of surrounding tissue, often surrounded by red, swollen, and tender skin
A wheal-and-flare reaction, often allergic in origin (hives), involving red, raised, pruritic, bumpy skin lesions
Lesions that exude a liquid, often in very small droplets
The evaluation of patients who complain of itching should include assessment for the presence of skin lesions, which potentially could be self-inflicted from scratching or skin picking. Psychiatrists, in particular, should be alert to phenomena such as delusional parasitosis or somatoform pain disorders that involve complaints about unusual skin sensations. Skin picking that can cause excoriated lesions (dermatillomania) is less likely to be iatrogenic than to be a manifestation of underlying conditions such as impulse control disorders, body dysmorphic disorder, and obsessive-compulsive or other anxiety disorders.
Drugs known to cause pruritus include opiates, aspirin, NSAIDs, and drugs that may cause hepatotoxicity. Clinicians should consider whether an allergic, pruritic contact dermatitis is caused by environmental exposure (e.g., to cosmetics, detergents, rosins, epoxy resins). Psychotropic drugs (other than opiates or synthetic opiates such as tramadol) rarely cause pruritus apart from idiosyncratic hypersensitivity reactions. In fact, some SSRIs have been reported to improve pruritus associated with lymphoma, uremia, cholestasis, and opiate use. Similarly, some antipsychotics with antihistamine effects (notably, promethazine begun at a dosage of 25 mg/day) are often referred to as antiallergic neuroleptics for the treatment of pruritus.
Nonsedating antihistamines such as loratadine or cetirizine are generally safe interventions for nonspecific pruritus. Sedating antihistamines such as hydroxyzine (25–100 mg at bedtime) or doxepin (10–25 mg at bedtime) may be especially useful not only to counteract the degranulation of mast cells in suspected allergic reactions but also for their anxiolytic properties. Pruritus also may be managed with the use of hypoallergenic, nonalcohol-based skin lubricants; menthol-camphor-based topical agents (e.g., Sarna lotion); or Aveeno oatmeal bath treatments.
Any drug can cause a skin rash, either from an allergic or a hypersensitivity reaction. Rashes should be evaluated to determine their location, appearance, and probable association with a suspected causal agent. Drugs suspected of causing a serious drug rash should be immediately discontinued, and appropriate dermatological evaluation should be obtained.
Psychiatrists may feel ill equipped to evaluate potential medication-related skin rashes and to incorporate into their practice a working knowledge of the nature and characteristics of common skin rashes caused by psychotropic drugs. Although seeking formal consultation from a dermatologist for certain types of rashes is often helpful, psychiatrists can and should be familiar with the language used to describe the appearance of skin rashes, perform an initial assessment, and form an impression about likely associations with prescribed psychotropic medications on the basis of time course and appearance.
Upon discovering a skin rash, practitioners should obtain a basic patient history that identifies where the rash appears to be, when it began, what current medications are being taken (and whether doses or adherence have deviated from prescribed recommendations), and whether other novel environmental exposures (including concomitant medications, botanicals, animals, insect bites, or skin care products) may be contributing factors. One should also consider whether there has occurred a recent change in formulation or preparation of an existing medication within a treatment regimen, because rashes could reflect reactions to excipients rather than active drug ingredients (e.g., in a new generic formulation of an existing drug).
Allergic drug rashes usually arise within several days to a few weeks after beginning a medication. True allergic reactions are type I (immediate) hypersensitivity reactions mediated by IgE antibodies. These reactions require prior exposure to an allergen that sensitizes mast cells and basophils, which, upon reexposure, degranulate and cause the release of histamine, leukotrienes, and prostaglandins that cause an inflammatory reaction. Drug rashes are highly unlikely to arise for the first time after many months (or years) of stable exposure. A further consideration involves the potential for an allergic reaction to the vehicle coating the active drug (rather than the drug itself). If a rash occurs, the clinician should consider whether it is a possible idiosyncratic reaction in the aftermath of renewing an existing prescription, changing the formulation (e.g., from extended to immediate release), or substituting a generic for a branded product formulation.
A next step involves describing the appearance and location of a rash. Appropriate terminology for describing the appearance of suspected drug rashes is presented in Table 8–1, and common types of skin rashes are described in Table 8–2.
The most commonly encountered true drug rashes appear on the trunk and are exanthematous or morbilliform in appearance. Attention should be paid to whether the area is flat or raised, bumpy, red, and weepy or dry. An urticarial wheal-and-flare rash should be identified as a probable allergic reaction, and the patient should be assessed for other potentially serious manifestations of impending anaphylaxis, such as laryngeal constriction or shortness of breath. Rashes that occur in a dermatomal (often linear) distribution not crossing the midline are suggestive of varicella or herpes zoster (shingles); zoster classically manifests with painful pruritic or tingling vesicular lesions but may also be nonraised or pruritic. Antiviral drugs such as oral acyclovir tend to be most effective when begun within 48–72 hours after symptom onset and continued until crusting has occurred. Purpuritic (i.e., nonblanching red or purple skin discolorations) nodular or ulcerative rashes that are accompanied by systemic symptoms (e.g., fever, fatigue, weakness or numbness, myalgias or arthralgias) may suggest a vasculitis or infectious process rather than a typical drug reaction. While most vasculitides have idiopathic, infectious, or inflammatory etiologies, a handful of medications have been described in connection with their development, including sulfonamide (and other) antibiotics, NSAIDs, coumadin, and thiazide diuretics.
Likely drug associations
Acne (as caused or exacerbated by medications)
Red papules and pustules
Lithium may cause or exacerbate
Oral or topical antibiotics; benzoyl peroxide cream or lotion; tretinoin (Retin-A)
Red (inflammatory) diffuse facial rash
Oral or topical antibiotics to help reduce episodes
Atopic dermatitis (a type of eczema)
Scaly, itchy, red areas commonly affecting the face, neck, elbows, inner knees, and ankles; may burn or itch
Topical hydrocortisone, betamethasone, or fluticasone creams or ointments commonly recommended
Bacterial rashes (e.g., impetigo, caused by local staphylococcal infection)
Red, itchy, patchy skin areas that become pustular
Topical antibiotics often ineffective; may require oral antibiotics
Skin irritation usually caused within 12–24 hours of reexposure to a specific allergen, following an initial exposure (sensitization); represents a type IV (delayed-type hypersensitivity [non–antibody-mediated]) reaction; typically manifests as papular, vesicular, scaly lesions
Medium- to high-strength topical steroid ointments
Fungal rashes (e.g., candida)
Scaly, exfoliative appearance, or may appear within skin folds (e.g., under the breast, inner groin) as red, flat, and tender to touch; may have small pustular edges
Antifungal topical creams (e.g., clotrimazole 1% or terbinafine 1%)
Hives or urticaria
Raised, itchy, wheal-and-flare reaction; may blanch; usually but not necessarily an allergic reaction; represents a type I (IgE-mediated) hypersensitivity reaction
Heritable condition involving red or pink, dry, flaky, patchy, or raised skin areas, usually nonpruritic; commonly affecting knees, elbows, and scalp
Lithium often may exacerbate; less commonly (case reports) associated with carbamazepine, divalproex, fluoxetine, paroxetine
Topical corticosteroids, vitamin D creams (e.g., calcipotriene), topical retinoids, inositol, salicylic acid, coal tar, ultraviolet light, or psoralen plus ultraviolet A (UVA) light (PUVA)
Red or purple nonblanching discolorations <1 cm in diameter caused by bleeding under the skin, commonly resulting from infection, vasculitis, coagulopathies, or platelet disorders
Carbamazepine; otherwise unlikely except with other drugs that cause immunologically mediated thrombocytopenia
Discontinuation of suspected causal agents and treatment of underlying vascular, platelet, or coagulation disorders
Red, itchy, exfoliative rash that affects skin areas containing sebaceous glands (scalp, face, and trunk)
Divalproex (incidence 1%–5%)
Medicated shampoos, topical antifungal agents (e.g., ketoconazole, clotrimazole), or topical steroids
Systemic condition and dermatological emergency that usually involves blistering, burnlike lesions on oral and other mucocutaneous tissues, accompanied by fever, fatigue, and pharyngitis
May be caused by bupropion, carbamazepine, chlorpromazine, divalproex, lamotrigine, venlafaxine
Cessation of causal agent; systemic steroids sometimes administered early in the course of illness; monitoring of electrolytes; avoidance of suprainfections or sepsis
Viral rashes (e.g., shingles caused by varicella or herpes zoster)
Variable appearance and characteristics; shingles follows dermatomal distributions; postviral exanthematous rashes may involve diffuse tiny red bumps that may or may not be pruritic
Treatment of underlying disease process
Xerosis (dry skin)
Dry, dull, flaky skin with visible fine lines
Nonprescription emollients (e.g., Lubriderm or Eucerincream or lotion)
Note. IgE=immunoglobulin E.
aStevens-Johnson syndrome is considered a milder variant of toxic epidermal necrolysis.
Common topical steroids that are sometimes used to treat rashes such as contact dermatitis are summarized in Table 8–3, grouped by relative strength.
Lithium-associated psoriasis has been reported to improve with the use of 4–6 g/day of omega-3 fatty acids or inositol 3–6 g/day. Case reports have indicated that atopic dermatitis and nondrug-induced psoriasis are responsive to treatment with bupropion.
Clinicians sometimes wonder whether a history of a drug rash with a particular medication class may help to predict the likelihood of the patient’s developing a future rash with a drug that has not previously been taken (e.g., due to cross-sensitivity). For example, a history of rashes with other anticonvulsants has been shown to confer a 3-fold increased risk for developing a nonserious rash with lamotrigine (Hirsch et al. 2006), although a history of prior anticonvulsant-associated rashes appears less predictive for developing a rash with lamotrigine than with other anticonvulsants (Alvestad et al. 2008). According to the manufacturer of lamotrigine, a history of rash with penicillin or sulfa antibiotics increases the risk for nonserious rashes with lamotrigine.
Serious Rashes and DRESS Syndrome
Serious rashes require immediate evaluation and determination of the presence of an allergic reaction that could progress to anaphylaxis, a nonallergic systemic hypersensitivity reaction for which a suspected causal agent should be promptly discontinued, or an altogether unrelated phenomenon that may require independent medical management (e.g., poison ivy, shingles). The time course for developing a rash represents one element of its evaluation, because rashes that occur many months or years after drug initiation are unlikely to be iatrogenic. Serious rashes have been recognized in particular with lamotrigine and with carbamazepine—both of which carry boxed warnings in their manufacturers’ product information materials regarding the potential for developing a serious rash. Additionally, a relatively small number of pediatric patients receiving the wakefulness-promoting agent modafinil for attention-deficit disorder (ADD) developed serious rashes, which prevented the FDA from granting approval of modafinil for children and adolescents with ADD.
Betamethasone dipropionate 0.25% (Diprolene)
Clobetasol propionate 0.05% (Temovate)
Diflorasone diacetate 0.05% (Psorcon)
Halobetasol propionate 0.05% (Ultravate)
Amcinonide 0.05% (Cyclocort)
Desoximetasone 0.25% (Topicort)
Fluocinonide 0.05% (Lidex)
Halcinonide 0.05% (Halog)
Betamethasone dipropionate 0.05% (Diprosone)
Fluticasone propionate 0.005% (Cutivate)
Mometasone furoate 0.1% (Elocon ointment)
Triamcinolone acetonide 0.5% (Kenalog, Aristocort C cream)
Fluocinolone acetonide 0.01%–0.2% (Synalar, Synemol, Fluonid)
Flurandrenolide 0.05% (Cordran)
Hydrocortisone butyrate 0.1% (Locoid)
Hydrocortisone valerate 0.2% (Westcort)
Mometasone furoate 0.1% (Elocon cream, lotion)
Triamcinolone acetonide 0.1% (Kenalog, Aristocort R ointment)
Desonide 0.05% (Tridesilon, DesOwen ointment)
Fluocinolone acetonide 0.025% (Synalar, Synemol cream)
Fluticasone propionate 0.05% (Cutivate cream)
Hydrocortisone valerate 0.2% (Westcort cream)
Triamcinolone acetonide 0.1% (Kenalog, Aristocort R cream, lotion)
Desonide 0.05% (DesOwen cream, lotion)
Fluocinolone acetonide 0.01% (Capex shampoo, Derma-Smoothe/FS)
Prednicarbate 0.05% (Dermatop cream, ointment)
Triamcinolone acetonide 0.025% (Aristocort A cream, Kenalog lotion)
Hydrocortisone 1% (nonprescription)
Hydrocortisone 2.5% (nonprescription)
The DRESS syndrome (Drug Rash [or Reaction] with Eosinophilia and Systemic Symptoms) is an example of a hypersensitivity syndrome (for further discussion, see Chapter 20, “Systemic Reactions”) in which systemic symptoms (e.g., fever, lymphadenopathy, inflammation) arise in conjunction with a morbilliform or maculopapular rash, usually arising 2–8 weeks after drug exposure. DRESS syndrome has been linked with several anticonvulsants as well as a number of other agents, as described below.
The incidence of either Stevens-Johnson syndrome or toxic epidermal necrolysis during treatment with carbamazepine (■) has been reported by the manufacturer as 1 per 500,000 patients. Notably, individuals of Han Chinese ancestry have been shown to carry an increased risk for developing carbamazepine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis in association with the HLA-B*1502 allele, which may represent a risk allele for which the FDA has recommended genotyping among Han Chinese Asians. With carbamazepine, as with lamotrigine, the risk for developing a serious skin rash is highest in the first few months of treatment.
Serious, life-threatening rashes—including Stevens-Johnson syndrome and toxic epidermal necrolysis—were observed in early studies of lamotrigine dosed aggressively for pediatric epilepsy. Subsequent studies identified that the risk for serious rashes with lamotrigine (■) appears highest when the dose escalation schedule occurs faster than recommended by the manufacturer (the recommendation is 25 mg/day for 2 weeks, followed by 50 mg/day for 2 weeks, then 100 mg/day for 1 week, then 200 mg/day; when combined with divalproex, dose escalation should occur at half this rate [i.e., 12.5 mg/day for 2 weeks, followed by 25 mg/day for 2 weeks, then 50 mg/day for 1 week, then 100 mg/day]). Divalproex delays phase II metabolism (glucuronidation) of lamotrigine, effectively increasing its levels and bioavailability. Risks of serious rashes also are higher when lamotrigine is coadministered with divalproex (particularly if the aforementioned dosing adjustment is not made) or when lamotrigine is used in children and adolescents. The risk for significant rashes appears to be highest during weeks 2–8 of treatment. Serious rashes typically involve blistering or burnlike lesions on soft, mucocutaneous tissues (as found in the oral cavity, nares, or conjunctivae) or skin exfoliation on the palms of the hands and soles of the feet. Systemic involvement often occurs, in which case patients may experience fever, malaise, lymphadenopathy, muscle pain, or facial edema. Serious rashes must be contrasted with benign rashes, which may occur on the extremities or trunk and are more often exanthematous (maculopapular), nonblanching, and nonpruritic.
The mechanism by which lamotrigine can cause serious rashes as part of a hypersensitivity syndrome is not well understood. Unlike delayed-type hypersensitivity reactions, the DRESS syndrome does not require prior exposure to the drug because the rash does not occur from a reactivation of sensitized mast cells and basophils.
Some authors have suggested undertaking dermatological precautions to minimize the risk for developing false-positive rashes that could be misattributed to lamotrigine rather than other more likely causes. Such precautions include avoiding exposure to other new medications or foods, cosmetics, deodorants, detergents, fabric softeners, sunburn, and environmental antigens such as poison ivy or poison oak. The potential for a rash to develop may also be diminished by avoiding the introduction of lamotrigine for 2 weeks following a prior rash, viral syndrome, or vaccination. Efforts such as these may lower the incidence of nonserious rash to about 5%.
Evidence suggests that patients taking lamotrigine who develop a nonserious rash that resolves after drug cessation may safely be rechallenged with lamotrigine, without recurrence of rash, by using a conservative dosing titration schedule (e.g., 5 mg every other day for 14 days, then increased every 14 days by 5 mg/day until reaching 25 mg/day, and thereafter following the manufacturer’s usual recommended dosing schedule) (Aiken and Orr 2010; Lorberg et al. 2009).
Serious rashes thought to result from use of lamotrigine warrant prompt drug cessation and evaluation by a dermatologist. Steroids are sometimes indicated for the treatment of Stevens-Johnson syndrome during early phases of the rash but are sometimes controversial because they may also delay recovery.
During randomized placebo-controlled trials of modafinil for the treatment of ADD in 933 children and adolescents, 12 cases of severe cutaneous reactions (possible erythema multiforme or Stevens-Johnson syndrome, with one case identified as being definite) were identified (Cephalon 2006). Subsequently, the FDA issued a “nonapprovable” letter regarding the pursuit by the manufacturer Cephalon of an ADD indication for modafinil in children and adolescents. The manufacturer ceased further efforts to obtain such an indication and did not conduct additional safety studies in children and adolescents with ADD. The risk of a serious dermatological reaction with modafinil in pediatric populations has been reported to be approximately 0.8%, with a median time to discontinuation (due to rash) of 13 days in clinical trials (manufacturer’s product information). Although rare, rash warrants consideration during off-label treatment in pediatric patients.
In 2014, the FDA issued a warning linking ziprasidone with DRESS syndrome based on six reported cases to the agency in which symptoms developed within 11–30 days after drug initiation. Ziprasidone should be stopped immediately if a DRESS reaction is suspected.
The symbol ■ is used in this chapter to indicate that the FDA has issued a boxed warning for a prescription medication that may cause serious adverse effects.