Management of Psychiatric Disorders in Patients with Stroke and Traumatic Brain Injury

INTRODUCTION

Psychiatric disorders are common after stroke and traumatic brain injury (TBI) both in the short term and long term. They can be caused by regional disruption of neuronal network, impairment of regional cerebral blood flow, impaired cerebral metabolism, axonal injury, and pressure effect of intracranial bleed. Around 16 million people each year experience first ever stroke. Of these patients, 5 million become disabled and 5.7 million dies.[1] Traumatic brain injuries are also common and pose an enormous burden on families and caregivers because of the associated neuropsychiatric complications.[2] However, these neuropsychiatric complications are often remained unaddressed or not adequately treated because of the treating doctor’s preoccupation with other severe physical disabilities, whereas treating these neuropsychiatric complications can improve the overall outcome of the patients to a considerable extent.

In this clinical practice guideline (CPG), the assessment of psychiatric disorders following stroke and TBI is discussed together, while the management of psychiatric disorders following stroke and TBI is discussed separately under the two broad subheadings. This CPG mostly focused on the most common neuropsychiatric consequences of stroke and TBI, namely depression, psychosis, anxiety, posttraumatic stress disorders (PTSD), mania, emotional lability, fatigue, apathy, and personality changes. There is substantial overlap between neuropsychiatric disorders following stroke and TBI and repetitions will be avoided. This CPG does not include the cognitive consequences of stroke and TBI. We included researches both on ischemic stroke and intracerebral hemorrhage. However, we did not include dementia.

CATEGORIES OF EVIDENCE AND STRENGTH OF RECOMMENDATIONS

While writing this CPG, we ensured compliance with AGREE II instrument. We marked available evidences from Ia to IV and strengths of recommendations from A to D as per the prevailing norms.[3]

Categories of evidence

• Ia: Evidence from meta-analysis of randomized controlled trials (RCTs)

• Ib: Evidence from at least one RCT

• IIa: Evidence from at least one controlled study without randomization

• IIb: Evidence from at least one quasi-experimental study

• III: Evidence from nonexperimental descriptive studies, such as correlation studies comparative studies, and case − control studies

• IV: Evidence from opinions and/or clinical experience of respected authorities or expert committee reports.

Strength of recommendations

• A: Directly based on Category I evidence

• B: Directly based on Category II evidence or extrapolated recommendation from Category I evidence

• C: Directly based on Category III evidence or extrapolated recommendation from category I or II evidence

• D: Directly based on Category IV evidence or extrapolated recommendation from Category I, II or III evidence

• S: Standard of care.

GENERAL ASSESSMENT OF PSYCHIATRIC DISORDERS FOLLOWING STROKE AND TRAUMATIC BRAIN INJURY

As a referral physician, psychiatrists have the role to make thorough assessment of a patient following stroke and TBI to rule in/out the presence of any psychiatric disorders in a busy emergency room or inpatient department or intensive care unit (ICU).

To assess the consciousness level of the patient, Glasgow Come Scale still remains the gold standard. It is usually very difficult to conduct a psychiatric assessment on a semi-comatose patient or a patient who is uncooperative. In that case, one can use Kirby’s pro forma for examining uncooperative patients. The attending psychiatrist should examine the patient in a calm environment with not too many people around. However, the presence of primary caregiver can be allowed if the patient cannot give reliable and valid information which is more often the case. The demeanor of the treating doctor should be nonthreatening. He should talk in a clear voice with every word being uttered with due stress to reach the patient who usually have some or the other sensory impairment. If in delirium, psychiatrist should revisit the patient at a later date and time. Psychiatrist should also take the pain to bring forth the history of substance use disorders which are commonly associated with road traffic accidents and resultant TBI [Box 1].

Box 1.

Checklist for treating psychiatrist while evaluating post stoke and posttraumatic brain injury psychiatric disorders

• Patient conscious, alert and cooperative

• Adequate clinical history

• Reliable informant who can be a primary care giver or eye witness

• History of preexisting psychiatric disorder

• History of SUDs

• Temporal correlation between stroke/TBI and onset of psychiatric disorders

• Biochemical investigations

• Neuroimaging, EEG

• Medicine chart

• BP, pulse rate, intake-output chart

• Detailed mental status examination (if uncooperative, Kirby’s pro forma for examining uncooperative patients should be used)

• Screening instruments for psychiatric disorders

• Liaison with neurologist, neurosurgeon

TBI – Traumatic brain injury; SUDs – Substance use disorders; EEG – Electroencephalography

The treating psychiatrist should go through the clinical records very carefully and if needed should corroborate the clinical history from the primary caregiver or the eye witnesses. Patient’s past psychiatric history is of immense importance as it has some correlation with development of poststroke depression (PSD) and other psychiatric disorders. Psychiatrist should also go through the laboratory reports carefully and look for underlying infection, blood loss, electrolyte disturbances, endocrine dysfunction, and other systemic comorbid conditions which are reflected in complete blood count, urine culture and sensitivity, cerebrospinal fluid study, hemoglobin level, serum sodium, serum potassium, serum chloride, serum thyroid-stimulating hormone, serum parathyroid hormone, fasting blood sugar, liver function test, serum creatinine, etc. If needed and when in doubt, the referral psychiatrist should order for more biochemical investigation to rule out organic condition. The psychiatrist should also pay attention to the neuroimaging reports (computed tomography scan, magnetic resonance imaging, etc.,) to decipher a possible connection between the neurological insult and psychiatric disorder. Electroencephalography should be ordered to rule out subconvulsive status epilepticus which can mimic a psychiatric disorder. A detailed scrutiny of the medications already received should be done to rule out any iatrogenic psychiatric disorder. If needed, the psychiatrist should talk to treating neurologist or the neurosurgeon regarding stoppage of medicine, replacing the offending drug, or possible dose adjustment.

A detailed mental status examination should be done with particular focus on obtaining an adequate speech sample, looking for the predominant affect, presence of any delusion or hallucination, and assessment of cognitive function, particularly judgment, abstract thinking, and lobar functions.

There are provisions to diagnose various psychiatric disorders following stroke, transient ischemic attack (TIA), and brain injury in DSM 5 and ICD10. The diagnosis of poststroke and post-TBI psychiatric disorders depends on structured clinical interview and using of a screening instrument. There is no universally accepted screening instrument for diagnosing psychiatric disorders following stroke or TBI. For the diagnosis of PSD, Beck Depression Inventory, Hamilton Depression Rating Scale, Nine-item Patient Health Questionnaire-9, Hospital Anxiety Depression Scale, Geriatric Depression Scale, and the Center for Epidemiological Studies Depression (CES-D) Scale have been used. Anxiety disorders can be screened by Hospital Anxiety and Depression Scale-Anxiety Subscale and Hamilton Anxiety Scale. For screening of PTSD, psychiatrist can use clinician administered PTSD Scale, PTSD checklist for a stressor, TIA or stroke as stressor; Post-Traumatic Stress Diagnostic Scale; Impact of Events Scale-Revised. Brief Psychiatric Rating Scale can be used for screening of psychosis and Young’s Mania Rating Scale can be used for screening of mania. For the assessment of personality disorders or personality changes, a detailed psychological evaluation with Eysenck’s Personality Questionnaire, Minnesota Multiphasic Personality Inventory, International Personality Disorder Examination, or Iowa Personality Disorder Screen may be needed [Table 1].

Table 1.

Screening tools and management of various psychiatric disorders following stroke/traumatic brain injury

Clinical condition	Name of screening instruments	Management
Poststroke/post-TBI depressive disorders	HADS	SSRIs, SNRIs and CBT
	BDI
	GDS
	HDRS
	PHQ-9
	CES-D
Poststroke/post-TBI anxiety disorders	HAS	SSRIs, SNRIs, TCAs, antipsychotics, anticonvulsants, anxiolytics, trauma-focussed therapies and CBT
	Hospital Anxiety and Depression Scale-Anxiety Subscale	SSRIs, SNRIs, TCAs, yoga, tai-chi, self-help mindfulness, and relaxation techniques
	Poststroke/post-TBI PTSD	PTSD checklist for a stressor, TIA or stroke as stressor
	Impact of Events Scale-revised
	Posttraumatic Stress Diagnostic Scale
	Clinician administered PTSD Scale
Poststroke/post-TBI psychosis	BPRS	SGAs e.g., quetiapine, risperidone and olanzapine, injectable antipsychotics, CBT for hallucination or delusion
Poststroke/post-TBI mania	YMRS	Mood stabilisers e.g., valproate, carbamazepine, oxcarbazepine etc.; antipsychotics e.g., olanzapine, quetiapine, risperidone etc., and benzodiazepines
Poststroke/post-TBI personality disorders	IPDE	Fluoxetine, citalopram, lithium, beta-adrenergic antagonists
	EPQ
	MMPI
	IPDS
Poststroke fatigue	FSS	Modafinil, regular physical exercises
	MAF
	VAS-F
Poststroke apathy	Apathy Scale	Nefiracetam, donepezil, bromocriptine, modafinil, methylphenidate, ropinirole and zolpidem
	Apathy Evaluation Scale

TBI – Traumatic brain injury; HADS – Hospital Anxiety Depression Scale; BDI – Beck depression inventory; GDS – Geriatric Depression Scale; HDRS – Hamilton Depression Rating Scale; PHQ-9 – Nine-item Patient Health Questionnaire; CES-D – Centre for epidemiological studies depression; SSRIs – Selective serotonin reuptake inhibitors; SNRIs – Serotonin norepinephrine reuptake inhibitors, CBT – Cognitive behavioural therapy; HAS – Hamilton Anxiety Scale; TCAs – Tri-cyclic antidepressants; BPRS – Brief Psychiatric Rating Scale; YMRS – Young’s Mania Rating Scale; SGAs – Second generation antipsychotics; IPDE – International personality disorder examination; EPQ – Eysenck’s personality questionnaire; MMPI – Minnesota multiphasic personality inventory; IPDS – Iowa personality disorder screen; FSS – Fatigue Severity Scale; MAF – Multidimensional assessment of fatigue; VAS-F – Visual Analog Scale–Fatigue; PTSD – Posttraumatic stress disorders; TIA – Transient ischemic attack

MANAGEMENT OF POSTSTROKE PSYCHIATRIC DISORDERS

Poststroke depression

PSD is the one of the most commonly reported neuropsychiatric conditions following stroke. Often undiagnosed, PSD is a treatable condition. PSD can occur within 1–18 months following stroke and its prevalence vary considerably over time (reported prevalence at 1, 3, 6, 12, and 18 months were 24.5%, 27.1%, 28.3%, 19.8%, and 26.3%, respectively).[4]

PSD is believed to be associated with worse functional outcome following stroke. A meta-analysis showed that, PSD had a adverse impact on survival rates following stroke and it affected short-term mortality more than long-term mortality.[5]

Various meta-analysis and systematic review have looked into the role of prophylactic antidepressant treatment to reduce the chance of developing PSD.[6,7,8,9] Many of them found that, selective serotonin reuptake inhibitors (SSRIs), cognitive behavioral therapy (CBT), and physical exercise improved mood symptoms in PSD.

A Cochrane review which included 63 RCTs and over 9000 participants and specifically looked into the role of SSRIs in PSD found that, SSRIs should not be used routinely to promote recovery after stroke as they do not improve recovery after stroke (A).[10] In the Effect of fluoxetine on functional outcomes after acute stroke trial, eligible patients with stroke were recruited and randomly given fluoxetine (20 mg daily) or placebo for 6 months, starting after 2 − 15 days of stroke. After 12 months of follow-up, fluoxetine was found to improve the neuropsychological scale score but not other variables. Therefore, it did not support the routine use of prophylactic fluoxetine in PSD (A).[11] Similar was the finding from the efficacy of citalopram treatment in acute stroke (TALOS study) (A).[12]

The efficacy of CBT on PSD remains undetermined due to low quality of the studies and high degree of heterogeneity among them as found by one meta-analysis (A).[13] Neuromodulation techniques such as transcranial direct current stimulation and transcranial magnetic stimulation can offer some benefit, but there are the lack of high quality RCTs (B).[14]

SSRIs and SNRIs are often used in conjunction with anti-platelet medication such as clopidogrel in PSD. Fluoxetine and fluvoxamine (CYP2C19 inhibiters) can reduce the efficacy of clopidogrel and can increase the risk of ischemic disease.[15] There have been concerns regarding intracranial bleed following the use of SSRIs also. Studies have suggested that, if given before stroke, SSRIs were associated with severity and mortality in patients with hemorrhagic stroke.[16] However, one recent review pointed out the lack of evidence in support of SSRIs alone increasing the risk of spontaneous intracranial bleed.

Therefore, it can be concluded that, SSRIs should not be prescribed prophylactically in all poststroke patients. Rather, they should be screened for PSD and if diagnosed, then only SSRIs and SNRIs can be prescribed as needed (S) with some sort psychological intervention (CBT) (B). Both neurologists and psychiatrists need to be aware of drug-drug interaction which can be potentially life threatening in such group of patients (S).

Poststroke psychosis

The symptoms of PSP include delusions, hallucinations, psychomotor agitation, irrelevant and incoherent speech, catatonic symptoms, and sleep cycle disturbances. These symptoms usually manifest within a week following stroke but may manifest several weeks later also. Studies form the early 90s indicated that PSP is relatively rare and after 9 years’ follow-up only 5 patients developed PSP.[17] A recent meta-analysis found the prevalence of PSP to be around 4.86%.[18]

Literature on the management of PSP is sparse compared to PSD or poststroke anxiety (PSA). RCTs on the management of PSP are lacking. The treatment usually follows same principles which are followed for the management and treatment of primary psychotic disorders. Second generation antipsychotics (SGAs), for example, quetiapine, risperidone, and olanzapine are most commonly used to treat PSP (D). However, their safety in patients with stroke is highly debatable. Olanzapine can have deleterious effect of plasma glucose and lipids which are not welcome in patients with stroke. Quetiapine can cause postural hypotension, whereas risperidone can cause extra-pyramidal side effects. The concern of anti-psychotics being associated with high incidences stroke has been refuted by a large case − control study.[19,20,21]

The usual practice is to start low and go slow in case of treatment of PSP (S). However, in certain cases (agitated and violent patients) injectables might be required and in that case injectable olanzapine or injectable haloperidol can be used (D). As in patients with primary psychotic disorders, CBT for hallucination or delusion can be beneficial in PSP (S).[22]

Poststroke anxiety disorders

PSA is common and only second to PSD in terms of prevalence. All kind of anxiety disorders can be seen following stroke but the core symptoms remain the same – palpitation, psychic and physical restlessness, excessive worry and fear, feeling of nervousness, pseudo neurological symptoms, for example, dizziness, blurring of vision, tingling and numbness of hands and feet, fine tremors, etc. Sensory impairment, ICU admission, painful physical conditions, communication difficulties, and sleep disturbance can lead to the development of PSA. A meta-analysis found the prevalence of PSA to vary between 20% to 24% depending on the time elapsed following stroke.[23]

SSRIs, SNRIs, Tri-Cyclic Antidepressants (TCAs), Mirtazapine, Buspirone, Benzodiazepines, and Z-drugs all have been used in the treatment of PSA in the absence of any definite guideline (D).[24] Meta-analyses conducted by Chun et al. reported beneficial effect of pharmacotherapy (paroxetine, imipramine, and buspirone) and psychotherapy compared to control. However, the studies were of low quality and highly heterogeneous, and therefore, the positive conclusion could be due to bias.[25] Cochrane review in this area also highlighted lack of quality studies and emphasized the need of large scale RCTs.[24] Nonpharmacological managements, for example, Yoga, Tai-Chi, Self-help mindfulness, and relaxation techniques can offer some benefit in the management of PSA (C).[26,27]

Therefore, SSRIs, SNRIs, and even TCAs can be used in the treatment of PSA (S, D) along with non-pharmacological interventions (C). However, as in case of PSD, psychiatrists and neurologists should be aware of potential drug-drug interactions.

Posttraumatic stress disorder following stroke

PTSD develops following an event which pose actual or imagined threat to physical and psychological integrity of an individual and stroke is no less than a catastrophe. Symptoms of PTSD include intrusive flashbacks/memories, autonomic arousal, emotional numbness, and avoidance behavior. Poststroke PTSD often has associated PSD and PSA (in up to 40% of the cases).[28] A meta-analysis reported 1-year prevalence of poststroke PTSD to be around 23%.[29] Furthermore, persons with PTSD have higher risk of developing stroke compared to people without PTSD.[30]

There is dearth of RCTs in treatment of PTSD. SSRIs, SNRIs, and TCAs can be tried (D). Other medications, e.g., antipsychotics, anticonvulsants, and anxiolytics have also been tried (D).[31] Psychotherapeutic approaches, e.g., trauma-focused therapies, CBT, and exposure therapy appears to be helpful in resolution of symptoms but they need to be tested in large scale studies (D).[32]

Poststroke mania

Prevalence of poststroke mania (PSM) is rather low (<2%).[33] Most of the data in this area are in the form of case report or case series.[33] Majority of the subject developed PSM between 1 day to 24 months after stroke.[34] In 1978, Kraut-hammer and Klerman gave the concept of secondary mania in which a manic episode is produced by metabolic, neurological, or toxic disorder.[34] The criteria of secondary mania (PSM in this case) are as follows: (1) symptoms lasting for at least 1 week; (2) presence of elevated or irritable mood; and (3) presence of at least two symptoms out of the followings: Pressured speech, grandiosity, hyperactivity, flight of ideas, distractibility, lack of judgment, and decreased sleep; and (4) no history of affective illness or delirium co-occurring with the mania. Lesions responsible for PSM are usually found in the caudate nucleus, parietal, temporal, and frontal lobes and thalamus. Mania is more common with right-sided lesions, although left sided lesions have also been reported.[35,36]

Treatment of PSM is in line with treatment of an acute manic episode. Mood stabilizers, e.g., valproate, carbamazepine, oxcarbazepine, etc.; antipsychotics, e.g., olanzapine, quetiapine, risperidone, etc.; and benzodiazepines are the mainstay of treatment (S. D). It is better to avoid lithium in this population because of the presence of multiple comorbidities and potential drug-drug interactions. Furthermore, choosing a mood stabilizer which allows antiepileptic coverage is beneficial.

Poststroke emotional lability

Poststroke emotional lability is also known by various other names, for example, pathological laughter/crying, emotional incontinence, hyperemotionality, pseudobulbar affect, etc. The symptoms appeared to be dramatic but transient. Patients can present with sudden onset laughter or crying while speaking on a rather inconspicuous matter. Sometimes, it may be difficult to differentiate it from depression. If symptoms are long-lasting, it may result in distress, depression, social avoidance, and embarrassment. The prevalence of poststroke emotional lability varies between 8% to 32%.[37]

Quality research in the management of poststroke emotional lability is lacking, thereby precluding any meaningful recommendation. A Cochrane review with total 293 participants reported, antidepressants reduced the frequency of laughing and crying episodes but the quality of evidence was low (A). The effect was not specific to any particular drug or class of drugs. The review pointed our several methodological deficiencies.[38]

Poststroke fatigue

Poststroke fatigue (PSF) is common sequalae of both ischemic and hemorrhagic stroke. Nearly half of the stroke survivors suffer from PSF. A systematic review put the prevalence of PSF between 25% and 85%.[39] Uniform definition of PSF is lacking. Most commonly PSF is described as, subject lack of mental and physical energy which interferes with individual’s day to day activities. PSF has been found to be associated with old age, neurological deficits, diabetes, hypertension, heart failure, kidney disease, pain, anxiety, depression, sleep disturbances, prestroke fatigue, and cognitive impairment.[40] Few studies have pointed to a link between PSF and subcortical and infra-tentorial infarcts.[40]

Considering the multifactorial causation of PSF, any one particular pharmacological agent is unlikely to provide any benefit. Modafinil, a mood awakener has been found to be useful in PSF following brainstem-diencephalic stroke because of its effect on reticular activating system (C).[41] A small RCT also favoured the use of Modafinil up to a dose of 400 mg/day (B).[42] SSRIs including fluoxetine, escitalopram, sertraline and SNRI, duloxetine has been studied in PSF but none were proven beneficial except for anxiety symptoms.[43,44] Clinicians often try vitamin supplementations in PSF. Vitamin B12, Vitamin B1, and idebenone, a synthetic coenzyme Q10 analog have all been studied, but results are inconclusive (C).[45,46,47] Joint American Stroke Association and American Heart Association statement encourages regular physical exercise to reduce PSF (D, S).[48] A Cochrane review which included two nonpharmacological interventions, mindfulness-based stress reduction program and a fatigue education program found no conclusive evidence of any intervention having any efficacy to treat PSF (A).[49]

Poststroke apathy

Post-stroke apathy is another frequent consequence of stroke. It is characterized by a lack of goal-directed behavior along with diminished cognition and emotion appetite. Recently, proposed diagnostic criteria for poststroke apathy includes: (a) diminished motivation for four weeks or more, and two other symptoms (reduced goal-directed cognitive activity, goal-directed behavior, or emotions), and functional impairments.[50] There are conditions, particularly depression, which can mimic poststroke apathy. In that case, emphasis should be put on presence/absence of cognitive symptoms of depression, for example, anhedonia, low mood, lack of attention and concentration, negative cognition, suicidal ideas, etc. Mean prevalence of poststroke apathy was 34.6% in a large meta-analysis.[51] Poststroke apathy is more common in less educated subjects, women, cognitively impaired, and in cases of recurrent stroke.[52] Apathy and depression co-occur in about 40% of cases.[51] Patients with poststroke apathy have been found to have higher risk of subsequent depression and worse functional outcome.[53]

Quality evidence for the treatment of poststroke apathy is lacking. There is one RCT with Nefiracetam (600 mg and 900 mg dose) which resulted in 4-point decrease in Apathy Scale score and more frequent remission (B).[54] Acetyl cholinesterase inhibitor, Donepezil has been found to have some benefit in poststroke apathy in a retrospective cohort study (C).[55] There are anecdotal evidences of bromocriptine, modafinil, methylphenidate, ropinirole, and zolpidem being effective in treating poststroke apathy in various case-reports (C).[51]

Poststroke personality disorders

There can be exacerbation of preexisting personality traits or patient can altogether develop new personality after a stroke. There are possibilities that patient becomes irritable/aggressive, disinhibited, and/or impulsive. Personality changes are more prominent in case of frontal lobe lesions. Studies have put the prevalence of irritability and disinhibition at 12%–53% and 6%–76%, respectively.[56,57] The wide variability in the prevalence was because of the setting in which the study was conducted, population chosen, type of stroke, and instruments used to assess personality changes.

There are very few RCTs which have looked into the treatment of poststroke personality disorders per se Data have been extrapolated from studies conducted in nonstroke individuals. SSRIs, for example, fluoxetine and citalopram can be beneficial for the management of aggression in patients with poststroke personality disorders (D).[58,59] Lithium and beta-adrenergic antagonists may also be effective to treat aggression in this group of patients (D).[60,61]

MANAGEMENT OF PSYCHIATRIC DISORDERS FOLLOWING TRAUMATIC BRAIN INJURY

For management of psychiatric disorders following TBI, we are not going to follow the same schema for stroke for brevity of this CPG. Rather, we will highlight upon important management issues and treatment evidences as deemed fit.

The first documented report of psychiatric disorder following TBI was of a construction worker called, Phineas Gage who survived an accident in 1848, when an iron bar penetrated his skull and damaged his frontal lobe which changed his personality form a socially adapted, responsible man to negligent, profane, and not willing to take responsibility.[62]

A variety of psychiatric disorders can be seen following TBI. Posttraumatic agitation, aggression, and irritability are common in coma-awakening period. Posttraumatic agitation has been related to posttraumatic amnesia, altered consciousness and decrease in cognitive function. The incidence of posttraumatic agitation varies between 11% to 70%.[63] Pain, ongoing medications, sleep deprivation, and underlying delirium can promote agitation. Aggression can be physical aggression and verbal aggression toward self and others. More often than not aggression is sudden and episodic in nature.[64] The extent of aggression is dependent upon the severity of initial injury and extent of prefrontal damage.[65] The incidence of aggression in TBI varies between 25% to 39%.[66] Irritability is although a rather muted form compared to agitation and aggression, it is common in post-TBI patients which manifests as excessive reaction with unjustified anger. The incidence of post-TBI irritability varies between 29% to 71% as per the nature of the studies conducted.[67]

Other disturbing consequences of TBI are apathy, abulia, and apragmatism. We have discussed apathy in detail in the section of psychiatric disorders following stroke. The prevalence of post-TBI apathy varies between 20% to 71%.[68] As discussed earlier, it may be difficult to differentiate apathy from depression. Furthermore, apathy can respond poorly to available pharmacological options.

Depression, anxiety, and psychosis are other common psychiatric disorders following TBI. The mean prevalence of depression after TBI was 7.5 times higher compared to general population and was put at 30%.[69] Being young, female, having depression at the time of suffering injury, preexisting cognitive deficits, lesion of left hemisphere (particularly basal ganglia and dorso-lateral prefrontal cortex and pain was associated with depression in TBI patients.[70] All kinds of anxiety disorders, for example, panic disorder, generalized anxiety disorder, agoraphobia, social anxiety disorder, obsessive compulsive disorder, and PTSD are common in TBI patients. The prevalence of anxiety disorders varies between 5.8% and 9.1% following TBI.[71] Association between psychosis and TBI is less clear. A meta-analysis suggested that, risk of schizophrenia was greater in TBI group as compared to the control group, but heterogenicity of studies included precluded any meaningful conclusion.[72] Suicidal ideation and attempts are higher in TBI group as compared to the general population and some researchers have found it to be as high as 3–4 times.[73] Around 20% participants with TBI expressed suicidal ideation.[74,75,76]

Almost all kinds of psychopharmacological agents, for example, mood stabilizers, antidepressants, antipsychotics, dopamine agonists, benzodiazepines, beta-blockers, and opioid receptor antagonists have been used in the treatment of psychiatric disorders following TBI [Table 2], but in the absence of robust study design and large sample size of the studies included, recommendations are difficult to make.[77,78,79,80,81,82,83,84,85,86,87,88,89,90,91,92,93,94,95,96,97,98,99,100,101,102,103,104,105,106,107,108,109] In clinical practice, many of these agents produce desired result, albeit temporarily, alone or in combination. There is scant evidence in favor of nonpharmacological treatment. One Cochrane review did not find any strong evidence in favor of any nonpharmacological intervention, for example, mindfulness-based cognitive therapy or CBT for depression following TBI.[110] There are certain things a psychiatrist should be aware while handling such patients, for example, level of consciousness, baseline cognitive function, neuroimaging findings, operative procedures done or pending, presence or absence of clinical seizure, subconvulsive status epilepticus, medications received by the patient, drug-drug interaction, family support, etc. [Box 2]. Minimum number of medications for minimum period should be prescribed to improve patient compliance (S). Benzodiazepines (oral or intramuscular) should be judiciously used because of risk of fall, fracture, and cognitive deterioration (S). Last but not the least, attending psychiatrist should also use his own judgment depending on presence/absence of comorbid physical conditions [Figure 1].

Table 2.

Pharmacological agents used to treat psychiatric disorders following traumatic brain injury and their strength of recommendation

Name of the molecule	Dose range	Clinical effect	Strength of recommendation
MPH[77]	3 mg/kg, two times daily	Increased the speed of information processing in several neuropsychological tests	B
Agomelatine[78]	25 mg at night	Increased efficiency of sleep	C
Modafinil[79,80,81]	300-600 mg/d	Improvement in fatigue but no improvement in excessive daytime sleepiness	A
Amantadine[82,83]	100 mg twice daily	Reduced frequency and severity of aggression and irritability	A
Valproate[84,85]	1000-2000 mg/day	Improvement in mood symptoms. Valproate should not be used prophylactically for posttraumatic seizures	B
SSRIs[86,87,88,89,90]	Variable dosages	Citalopram and sertraline should not be used for prevention of relapse of depressive symptoms after TBI Use of fluoxetine for 6 months in patients with posttraumatic stress decreased relapse rates MPH and sertraline had similar effects on depressive symptoms, however, MPH caused more improvement in cognitive functions	B
Venlafaxine[91]	75 mg twice daily	Improved obsessive-compulsive symptoms, irritability and sadness	C
Bromocriptine[92]	5 g, twice daily	Did not improve alertness, was associated with side effects	B
Rivastigmine[93]	3-6 mg/d	Was beneficial for moderate to severe memory impairment	B
Galantamine[94]	16-24 mg/d	Improved fatigue, initiative, attention and memory	B
Donepezil[95,96]	10-20 mg/d	Improved metabolism in all 4 lobes of brain, overall clinical improvement and memory improvement	B
Naltrexone[97,98]	50-100 mg	Improved initiation, attention and accuracy of answering nonverbal questions	C
Beta blockers (Propranolol)[99,100]	420-520 mg/d	Number of attempted assaults and agitated episodes decreased	A
IM Droperidol and Haloperidol[101,102]	IM droperidol 1.25-10 mg and IM haloperidol 2.5-10 mg	IM droperidol achieved faster calming compared to IM haloperidol	B
Clozapine[103]	300-750 mg	Marked decrease in aggression	C
Quetiapine[104]	25-300 mg	Reduction in aggression	B
Ziprasidone[105]	40-80 mg	Decrease in agitated behavior	C
Carbamazepine[106]	400-800 mg	Improvement in social disinhibition and agitation was noted	B
Lamotrigine[107]	50 mg	There was the decreased need for benzodiazepines to control outburst	C
Lithium[108]	900 mg/d	Decreased requirement of neuroleptics and decreased in aggression	C

TBI – Traumatic brain injury; MPH – Methylphenidate

Box 2.

Points to remember for treating psychiatrist in patients with traumatic brain injury

• Assess level of consciousness of the patient. Do a GCS scoring (S)

• Enquire about post-TBI loss of consciousness, ENT bleed, seizures

• Try to understand the nature of problem. It may be different for the patient and the caregiver

• If possible, get a baseline neurocognitive assessment done. In absence of the same, do a MMSE (S)

• Go through neuroimaging and EEG reports

• Go through the medications which he/she is already on

• If patient underwent neurosurgery, go through the OT notes/discharge notes

• Mention your clinical diagnosis or at least the provisional diagnosis. It may be required later because of medico-legal issues associated with such cases (S)

• Choose medication in such a way that it covers neurological issue and psychiatric issue simultaneously e.g., in a patient with seizure and aggression following TBI one can choose valproate which will be effective for both the conditions (S)

• Always encourage healthy lifestyle, exercise and mental activities

• Assess for SUD. If present, treat it like a case of dual diagnosis

GCS – Glasgow Coma Scale; ENT – Ear-nose-throat; MMSE – MiniMental State Examination; EEG – Electroencephalography; OT – Operation theater; SUD – Substance use disorders

Figure 1.

Flowchart of psychiatric management of a patient with traumatic brain injury

CONCLUSION

Psychiatric disorders following stroke and TBI present unique challenges for the treating psychiatrist. Being a physician who is dealing with brain disorders, psychiatrists of 21^st century should possess in depth knowledge of brain pathways, neurotransmitters and its function. On the other hand, being a behavioral scientist, he/she should be sensitive toward the disability of the patient, the need of the caregivers, and empathetic toward the emotional need of both. The link between psychiatric disorders following stroke and TBI is not an uncomplicated one. Therefore, treatment also needs to be individualized. No one drug fits for all. Psychiatrist often has to do permutation and combination before he/she finds the suitable match. As already been highlighted, there is dearth of large scale RCTs for most of the conditions and treatment recommendations are often extrapolated from primary psychiatry disorders. However, that always may not work. Because a compromised or injured brain may not function in the same way as a “normal” or “uninjured” brain. However, this guideline made an attempt to collate majority of the available evidences in this area and recommendations were made based on those evidences. Reader has to apply his/her own judgment while implementing this is in a particular clinical setting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.