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Depression, Psychosis, and Agitation in Stroke
Introduction
Every year, stroke affects more than 15 million patients worldwide, resulting in death in 5.7 million patients and disability in another 5 million . Neuropsychiatric disorders are common after stroke, including depression, anxiety, agitation, mania, apathy, emotional lability, psychosis, and fatigue ( Table 147.1 ). Noncognitive neuropsychiatric disorders are distressing to patients, families, and caregivers in the poststroke period, and can significantly interfere with rehabilitation efforts following a stroke . Moreover, these disorders have been shown to be associated with increased morbidity in the poststroke period. Despite their high prevalence and association with increased morbidity, these disorders remain underrecognized by health care professionals and may not always be adequately treated. We present the definition, clinical diagnosis, causes, and treatment of three of the most severe neuropsychiatric complications of stroke, i.e., depression, psychosis, and agitation. Common medications used for the treatment of the neuropsychiatric complications of stroke are summarized in Table 147.2 .
Table 147.1
Neuropsychiatric Complications of Stroke
| Neuropsychiatric Syndrome | Prevalence (%) | Putative Neuroanatomical Correlates |
|---|---|---|
| Depression | 30–35% at admission | No clear association established |
| 19–52% at 2 years | Major depression: left-frontal and left-basal-ganglia lesions | |
| Mania | ≤2% | Right-hemisphere, bifrontal, basotemporal, subcortical, midline, right-basal-ganglia, and right thalamus lesions |
| Bipolar Disorder | Rare | Right subcortical , right basal ganglia, and right thalamus lesions |
| Anxiety | 25–40% with depression | No clear association established |
| 6% without depression | With depression: left frontal cortical lesions | |
| Without depression: right parietal lesions | ||
| Emotional Lability | 8–32% | Frontal lesions |
| Agitation with Aggression | 6% | Left-anterior-lobe lesions |
| Fatigue | 23–75% | No clear associations established |
| Apathy | 35% | No clear associations established: possible associations with cingulate and subcortical structures (more common with bilateral lesions or unilateral lesions in the presence of a prior contralateral frontal lesion) |
| With depression: left frontal and basal ganglia lesions | ||
| Without depression: posterior internal capsule lesions | ||
| Personality Disorders | <1% | No clear association established |
| Psychosis and Psychotic Symptoms | <1–10% | No clear associations established, possibly more common with right-parietotemporal-occipital lesions |
| Pathological Laughing and Crying (Pseudobulbar Affect) | 20% | Bilateral hemisphere lesions |
| Catastrophic Reaction | 20% | Anterior cortical lesions |
| Anosognosia | 24–43% | Right-hemisphere lesions |
Table 147.2
Psychotropic Medications for the Neuropsychiatric Complications of Stroke a
| Neuropsychiatric Syndrome | Psychotropic Medication | Daily Dose (mg) | Initial Dose (mg/d) | Dose Adjustment in Elderly or in Those with Medical Illness | Side Effects |
|---|---|---|---|---|---|
| Depression | Sertraline | 50–200 | 50 | Lower dose or less frequent dosing in hepatic impairment; elderly prone to hyponatremia with SSRIs; start at 12.5 mg/d in patients with Alzheimer disease | Diarrhea, nausea, headache, insomnia, sexual dysfunction, dizziness, dry mouth, fatigue, drowsiness |
| Citalopram | 40 | 20 | Daily dose should not exceed 20 mg in patients with hepatic impairment, in poor CYP2C19 metabolizers, or when coadministered with CYP2C19 inhibitors (e.g., cimetidine, fluconazole, omeprazole) because of the risk of prolonged QT interval Concomitant administration with linezolid and IV methylene blue is contraindicated because of the risk for serotonin syndrome; elderly prone to hyponatremia and long QT interval |
Dry mouth, nausea, sedation, insomnia Increased sweating Prolonged QT interval in higher doses |
|
| Mirtazapine | 15–45 | 15 | Initial dose 7.5 mg in the elderly Monitor closely in patients with renal and hepatic impairment |
Sedation, weight gain, increased appetite, constipation Agranulocytosis in 0.1% of patients |
|
| Bipolar Disorder Mania |
Lamotrigine | 100–400 (target dose for bipolar disorder is 200 mg without valproic acid use and 100 mg with valproic acid use) | Slow titration: 25 mg po qd for 2 weeks, then 50 mgpo qd for 2 weeks, and finally 100 mg po qd for 1 week; start at 25 mg every other day when used with valproic acid | Dose reduction by 25% in patients with hepatic impairment without ascites and 50% in those with ascites; dose reduction in cases of severe renal impairment | Dizziness, diplopia, headache, ataxia, blurred vision, sedation, rhinitis, and Stevens-Johnson syndrome in 0.3–0.8% of children and 0.08–0.3% of adults when used with valproic acid |
| Carbamazepine | 400–1600 (divided into bid or tid dosing) | 400 (divided into bid dosing) | Dose should be reduced by 25% in patients who are on hemodialysis or with GFR <10 mL/min; caution is necessary in patients with hepatic impairment | Ataxia, dizziness, drowsiness, nausea/vomiting, SIADH, Stevens-Johnson syndrome | |
| Valproic acid | 750–1500 (maximum dose 60 mg/kg/d) | 750 mg/d in divided doses (25 mg/kg/d for extended release) | Lower dose and slower titration in elderly and in patients with hepatic impairment, contraindicated in cases of severe hepatic impairment | Nausea/vomiting, headache, low platelet count, tremor, alopecia, sedation, ataxia, nystagmus, weight gain, acne, Stevens-Johnson syndrome, high ammonia levels, pancreatitis, increased levels of liver transaminases | |
| Lithium | 900–2400 (divided into tid or qid dosing) | 900 mg (divided into tid or qid dosing) | Lower doses in elderly | Leukocytosis, polyuria/polydipsia, hand tremor, ataxia, hypothyroidism (1–4%), confusion, memory impairment, headache | |
| Anxiety | Sertraline | 25–200 | 25 | Lower dose or less frequent dosing in patients with hepatic impairment; elderly prone to hyponatremia with SSRIs; start at 12.5 mg/d in patients with Alzheimer disease | Diarrhea, nausea, headache, insomnia, sexual dysfunction, dizziness, dry mouth, fatigue, drowsiness |
| Paroxetine | 10–60 | 10 | 10 mg/d not to exceed 40 mg/d in cases of severe renal impairment (CrCl <30 mL/min); sedation and anticholinergic effects in elderly; elderly prone to hyponatremia | Nausea, insomnia, dry mouth, headache, asthenia, constipation, diarrhea, dizziness, sexual dysfunction, tremor | |
| Buspirone | 10–60 | 10–15 (divided into bid or tid dosing) | Not recommended in cases of severe renal or hepatic impairment | Dizziness | |
| Fatigue | Amantadine | 200–400 (divided into bid, tid, or qid dosing) | 200 (divided into bid dosing) | Dose adjustment in renal disease: 100 mg every day if CrCl is 30–50 mL/min, 100 mg every other day if CrCl is 15–29 mL/min, and 200 mg every week if CrCl <15 mL/min | Anxiety, anorexia, constipation, depression, peripheral edema, livedo reticularis, dry mouth, insomnia with bedtime dosing |
| Apathy | Methylphenidate | 20–60 | Immediate release form: 20–30 mg divided into bid or tid dosing | Contraindicated with glaucoma or within 2 weeks of use of MAO inhibitors, use cautiously with hypertension, heart failure, drug dependence, and alcoholism | Headache, hypertension, nausea, nervousness, psychosis, seizures, tachycardia, arrhythmias, risk of drug abuse and dependence, withdrawal associated with depression |
| PsychosisAgitation with AggressionCatastrophic Reaction | Quetiapine | 150–750 (immediate release) 400–800 (extended release) |
50 | 25–200 mg in elderly (initially 25–50 mg/d); Dose adjustment needed in patients with hepatic impairment | Extrapyramidal syndrome/tardive dyskinesia (+/−), sedation (++), anticholinergic effects (dry mouth, constipation, urine retention) (++), orthostasis (++), prolonged QT interval (+), weight gain, hyperglycemia, hyperlipidemia, increased diastolic blood pressure, headache |
| Olanzapine | 10–20 | 5–10 | Initially 1.25–2.5 mg/d; typical maintenance dose is 5 mg/d; maximum 10 mg/d | Extrapyramidal syndrome/tardive dyskinesia (+), sedation (++), anticholinergic effects (dry mouth, constipation, urine retention) (++), orthostasis (+), prolonged QT interval (+), weight gain, hyperglycemia, hyperlipidemia, increased ALT, high prolactin | |
| Risperidone | 2–6 | 1–2 | Initially 0.25–0.5 mg/d; typical maintenance 1 mg/d; maximum 2 mg/d; dose adjustments are needed in patients with renal and hepatic impairment | Extrapyramidal syndrome/tardive dyskinesia (+++), sedation (+), anticholinergic effects [dry mouth, constipation, urine retention] (+), orthostasis (+), prolonged QT interval (+), weight gain, hyperglycemia, hyperlipidemia, increased ALT levels, high prolactin levels | |
| Pseudobulbar Affect | Dextromethorphan/quinidine | One capsule (20/10 mg) po bid | One capsule (20/10 mg) qd for 1 week | Safety not established in patients with severe renal or hepatic impairment, no dose adjustment needed for patients with mild or moderate renal or hepatic impairment | Diarrhea, dizziness, vomiting, cough, peripheral edema, increased GGT levels |
| Nortriptyline | 75–150 | 75–100 (divided into tid or qid dosing) | Initial dose is 30–50 mg/d and a maximum dose of 100 mg/d in elderly (given once a day or in divided doses) | Fatigue, sedation, dry mouth, constipation, orthostasis, tachycardia, seizures, SIADH |
ALT , alanine aminotransferase; bid , twice a day; CrCl , creatinine clearance; CYP2C19 , cytochrome P450 2C19; GFR , glomerular filtration rate; GGT , gamma-glutamyl transferase; IV , intravenous; MAO , monoamine oxidase; po , orally; qd , every day; qid , four times a day; SIADH , syndrome of inappropriate secretion of antidiuretic hormone; SSRIs , selective serotonin reuptake inhibitors; tid , three times a day ; qid , four times a day; (+/−), absent or negligible; (+), infrequent; (++), moderately frequent; (+++), frequent.
a Commonly used medications are listed in the table; the table is not intended to be inclusive of all medication options.
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