PSYCHIATRISTS PLAY AN essential role in the pretransplant evaluation and continuous care of liver transplant patients.1 The prevalence of mental disorders among post-liver-transplant patients has ranged from 30% to 70%, depending on the study sites, the time of investigation after transplantation, and the diagnostic criteria used.2–5 Although most of these disorders will remit by the time the patient is discharged from the hospital, acute treatment is imperative for the relief of painful experiences for patients and the family members involved. In Taiwan, orthotopic liver transplantation (OLT) was carried out from March 1983, followed by living-related living donor liver transplantation (LDLT) since June 1994.6,7 A multidisciplinary team with a psychiatric consultation–liaison (C–L) service has been set up for the management of psychiatric morbidity. The psychiatric C–L service could provide special knowledge about central nervous system complications after transplant and drug interactions between immunosuppressant and psychotropic medication.8,9 But are recommendations from psychiatric consultation followed?10,11 It has been reported that the surgeon has the highest concordance rate (62.3%) with the recommended psychotropic medications among all consultees in Taiwan.12 The patients with post-transplant psychiatric consultation are different in some aspects from other medical–surgical consultation inpatients.13 This report describes the clinical characteristics of referral inpatients who received liver transplantation and the surgeon's concordance with psychiatric consultation. Effects and limitations of psychiatric C–L services are discussed, with a comparison with earlier studies.
Aim: This report describes the clinical characteristics of referral inpatients who received liver transplantation and the surgeon's concordance with the psychiatric consultation.
Methods: During a 4-year period, psychiatric consultation was arranged for 30 post-liver-transplantation inpatients at Kaohsiung Chang Gung Memorial Hospital. A psychiatrist assessed these patients and made psychiatric diagnoses according to the Diagnostic and Statistical Manual, 4th edition. The clinical data were routinely collected via modified MICRO-CARES software. At the end of the 4-year study period, all the medical records of these 30 inpatients were reviewed.
Results: Psychiatric diagnosis was made in 70% of the patients (n = 21) in three major categories, including delirious state (n = 8), depressive disorder (n = 5), and anxiety/dyssomnia (n = 8). All these conditions were improved by psychiatric management. We found that the consultee's concordance with recommended drug prescriptions was high with antidepressants in depressive patients and low with antipsychotics in patients with delirium. Moreover, anxiolytics were frequently prescribed in post-transplant inpatients before psychiatric consultation.
Conclusion: These findings suggest that psychiatric consultation is beneficial to inpatients after liver transplantation, especially those with depression and delirium.
This study was carried out at Kaohsiung Chang Gung Memorial Hospital, a medical center with 2438 beds, located in Kaohsiung County, Taiwan. The investigators retrospectively evaluated 30 consecutive inpatients with a psychiatric consultation after liver transplantation from 1 October 2003 to 30 September 2007. All liver transplantations were performed following the Taiwan Organ Transplant Clause. They occupied 18% of all surgical inpatients with a psychiatric consultation (n = 168) during the study period. A C–L psychiatrist (N-M. C.) assessed these patients and made psychiatric diagnoses according to the Diagnostic and Statistical Manual, 4th edition (DSM-IV).14 Psychiatric management was also recommended. In some patients, a follow-up psychiatric consultation was requested. The clinical data were routinely collected via modified MICRO-CARES software.15 At the end of the 4-year study period, all the medical records of these 30 inpatients were reviewed. As these patients had good compliance with the surgeon, most of the important medical records were available in detail.
The medical records of study patients were carefully checked. Data analyzed included age, sex, time lag (days between liver transplantation and psychiatric consultation), main reasons for consultation, psychiatric diagnosis and drug recommendations, consultee's concordance with recommended medication, and the ratio between days under recommended psychotropic medication during hospitalization and days from consultation until discharge. The procedures were approved by the Ethical Committee of Human Experimentation in our country.
Psychiatric diagnosis was made in 21 (70%) patients (16 men, 5 women). Their age ranged from 35 to 66 years old, with a mean age of 52.6 ± 7.5 years. They were grouped into three main categories: ‘delirious disorder’ (n = 8), ‘depressive disorder’ (n = 5), and ‘anxiety/dyssomnia disorder’ (n = 8).
The eight inpatients with ‘delirious disorder’ included five cases with delirium due to their general medical condition and three cases with delirium due to sedative drug withdrawal and transplantation. Among the latter, two might have been derived from abrupt withdrawal of Lorazepam post-transplantation after long-term use for one year; one was diagnosed as having hypnotic withdrawal delirium post-transplantation (he had a previous history of alcohol dependence and had used a hypnotic drug to replace alcohol for more than one year). The five inpatients with ‘depressive disorder’ included one with major depression unrelated to the transplantation, one with dysthymia, one with depressive disorder due to her general medical condition, and two with depressive disorder, not otherwise specified. Their depressive symptoms included: anhedonia, dysphoric mood, feelings of helplessness, loss of self-esteem, and guilt.
The eight inpatients with ‘anxiety/dyssomnia disorder’ included one with adjustment disorder with mixed depressive and anxious mood, one with adjustment disorder with anxious mood, and six with dyssomnia. These patients obviously experienced a deteriorating physical condition, complications due to surgery and long-term stay in hospital. The nine inpatients without any psychiatric diagnoses were referred mainly for psychiatric evaluation before Interferon treatment for hepatitis C.
Table 1 shows age, sex, referral lag, main reasons for consultation, psychiatric diagnosis and recommended drug, consultee's concordance with recommended medication, the ratio of days for taking the recommended psychotropic drug during hospitalization and days from consultation day until discharge day.
|Patient No.||Sex||Age||Referral lag||Reasons for consultation||Psychiatric diagnosis||Recommended drug||Concordance with drug||Days 1/Days 2|
|Delirium 1||M||53||8||Irritable mood and delirium||Drug Withdrawal Delirium||Lorazepam||Yes||25/41|
|Delirium 2||M||56||13||Irritable mood||Delirium||Quetiapine Lorazepam||Yes||13/56|
|Delirium 3||F||56||6||Weakness, general soreness||Delirium||Haloperidol Lorazepam||Yes||3/46|
|Delirium 4||M||47||9||Mutism, destructive behavior||Delirium due to drug withdrawal/transplant, in remission||Lorazepam||Yes||1/16|
|Delirium 5||M||49||8||Confusion||Delirium||Quetiapine Lorazepam||No||1/27|
|Haloperidol 1amp IM stat Lorazepam|
|Delirium 6||M||52||6||Acute psychosis||Delirium||Quetiapine||No||1/27|
|Delirium 7†||M||59||26||Confusion and poor memory||Delirium due to drug withdrawal/transplant||Quetiapine||No||8/10|
|Delirium 8||M||56||11||Irritable mood||Delirium||Quetiapine||No||14/24|
|Depression 1||M||58||270||Insomnia||Dysthymic Disorder||Mirtazapine Lorazepam||Yes||103/103|
|Depression 2||F||54||5||Irritable and depressed mood||Depressive Disorder||Mirtazapine Lorazepam||Yes||29/29|
|Depression 3||M||39||6||Insomnia||Depressive Disorder||Mirtazapine Lorazepam||Yes||6/91|
|Depression 4†||M||55||215||Insomnia, Past depression history||Major Depressive Disorder||Mirtazapine Clonazepam Zolpidem||Yes||18/18|
|Depression 5†||F||66||211||Multiple somatic discomforts||Depressive Disorder due to medical condition||Mirtazapine Lorazepam||Yes||15/15|
|Anxiety 1‡||M||35||216||Depression due to worse liver function||Adjustment Disorder With Anxiety and Depression||No drug use||Yes||0/17|
|No drug use|
|Anxiety 2||M||56||373||Insomnia and FK-506 effect evaluation||Dyssomnia||Lorazepam||No||19/19|
|Anxiety 3||M||39||131||Anxiety for complication and long hospitalization||Adjustment Disorder With Anxiety||Lorazepam||Yes||4/4|
|Anxiety 4||M||58||60||Insomnia and FK-506 effect evaluation||Dyssomnia||Lorazepam||Yes||32/32|
|Anxiety 6||F||60||69||Evaluation before Interferon treatment||Dyssomnia||Lorazepam||No||0/21|
|No drug use|
|Anxiety 7||M||47||498||Evaluation before Interferon treatment||Dyssomnia||No drug use||Yes||0/1|
|No drug use|
|Anxiety 8†||F||56||155||Evaluation before Interferon treatment||Dyssomnia||Lorazepam||No||0/17|
|No drug use|
Table 2 shows the main reasons for consultation, coincidental psychiatric disorder, concordance with recommended drug, psychotropic medication prescription, days for taking psychotropic drug during hospitalization among the three groups of patients with first-time psychiatric referral post-liver-transplant.
|Characteristics||Patients with delirium||Patients with depression||Patients with anxiety/dyssomnia|
|n = 8||n = 5||n = 8|
|Sex (M : F)||7:1||3:2||6:2|
|Age (Mean ± SD)||53.8 ± 3.6||50.4 ± 9.2||50.4 ± 9.2|
|OLT : LDLT||2:6||2:3||1:7|
|Referral lag post-transplantation||10.9 ± 6.6||141.4 ± 126.2||203.6 ± 154.8|
|Main referral reasons by consultee|
|Confusion/delirium||4 (50.0%)||0 (0%)||0 (0%)|
|Irritable/destructive behavior||3 (37.5%)||0 (0%)||0 (0%)|
|Somatic discomforts||1 (12.5%)||1 (20.0%)||0 (0%)|
|Depression||0 (0%)||1 (20.0%)||1 (12.5%)|
|Insomnia/anxiety||0 (0%)||3 (60.0%)||4 (50.0%)|
|Evaluation before Interferon||0 (0%)||0 (0%)||3 (37.5%)|
|Psychiatric disorder history||3 (37.5%)||1 (20.0%)||0 (0%)|
|Concordance with recommended drug||4 (50.0%)||5 (100.0%)||5 (62.5%)|
|Antipsychotic drug||2 (25.0%)||2 (40.0%)||0 (0%)|
|Antipsychotic drug prescription before consultation||1 (12.5%)||0 (0%)||0 (0%)|
|Antidepressant drug||0 (0%)||5 (100.0%)||0 (0%)|
|Antidepressant drug prescription before consultation||0 (0%)||0 (0%)||0 (0%)|
|Anxiolytic/hypnotic drug||8 (100.0%)||5 (100.0%)||4 (50.0%)|
|Anxiolytic drug prescription before consultation||6 (75.0%)||5 (100.0%)||2 (25.0%)|
|Days for taking psychotropic drug during hospitalization||8.3 ± 8.6||37.6 ± 38.7||48.6 ± 65.7|
|Hospitalization days||48.4 ± 22.0||55.4 ± 32.1||48.8 ± 33.4|
Of all referral inpatients, 18 (60%) received psychotropic drugs. Although a C–L psychiatrist suggested an antipsychotic drug for six inpatients with delirium, a consultee followed this recommendation only for two of these patients. A consultee prescribed anxiolytic drugs for the other two inpatients with delirium following a C–L psychiatrist's suggestion. The total concordance with medication recommendation among inpatients with delirium was 50.0% (4 of 8).
Surgeon consultees prescribed an antidepressant (Mirtazapine) for all of the five inpatients with ‘depressive disorder’ following a C–L psychiatrist's recommendation. The total concordance with medication recommendation among inpatients with ‘depression related disorder’ was 100.0%.
Among the eight patients with ‘anxiety/dyssomnia disorder’, three were diagnosed while they were referred for a depression evaluation before Interferon treatment for hepatitis C. A C–L psychiatrist didn't recommend medication for dyssomnia in one of them because of his concern for the patient's deteriorating liver function. The other two cases didn't take any medication for dyssomnia because of the consultee's concern for their liver function. One patient, for whom a C–L psychiatrist didn't recommend any medication, recovered from temporary anxiety and depressive symptoms after he received a liver transplantation for the second time. Of all eight patients, only three took anxiolytic (Lorazepam) for dyssomnia and only two didn't take a drug for dyssomnia under the C–L psychiatrist's recommendation. The total concordance with consultation recommendation among inpatients in this group was 62.5% (5 of 8).
All patients with depression (100%) had good concordance with medication recommendation. This result was better than the other two groups (50% of patients with delirium and 62.5% of patients with anxiety/dysomnia), but the difference is not statistically significant (Fisher's exact test, P = 0.1861).
Surgeon consultees prescribed anxiolytics for all of the eight delirious patients, all five depressive patients, and four (50.0%) patients with anxiety/dyssomnia. Interestingly, anxiolytic prescription before the psychiatrist's visit was seen in six (75.0%) delirious patients and five (100%) depressive patients. But only two (25.0%) anxious/insomnia patients received the anxiolytic drug before the psychiatrist's visit. An antipsychotic drug was prescribed for only one (12.5.0%) delirious patient and no antidepressants were prescribed for depressive patients before psychiatric consultation.
Days on psychotropic medication during hospitalization were related to the number of days spent hospitalized. Depressive patients had the longest hospital stays; while delirious patients had the shortest stays among the three groups.
Five referral patients received repeated psychiatric consultation because of new problems detected by surgeons. One patient without any psychiatric diagnosis at first referral developed pain disorder and depressive disorder that necessitated repeated psychiatric consultation. One patient with severe major depression had been repeatedly referred to a psychiatrist and was finally hospitalized to the psychiatric ward during the study period. This patient responded well to electroconvulsive therapy after a poor response to antidepressants with antipsychotic drug augmentation. The other three patients had initially been diagnosed as being in a delirious state. Two of them were diagnosed as having major depression and one with dyssomnia at the secondary psychiatric consultation. The condition of all the patients improved after the appropriate psychiatric intervention. Finally, 13 inpatients still received anxiolytic drugs at discharge and five of them visited the psychiatric clinic later.
In Taiwan, a C–L psychiatrist was consulted to evaluate active alcohol or illegal drug dependence, psychotic disorders and personality disorders before organ transplantation. Hence, these disorders were not found in this study.16–18 Kishi et al. reported that post-transplant patients have less psychiatric history than non-transplant patients.13 However, stable psychiatric patients with long-term hypnotic dependence and/or major depressive disorder were not absolutely contraindicated for liver transplantation, and were not easily recognizable by the surgeon. This may explain why the three cases with hypnotic dependence were not referred to a C–L psychiatrist before transplantation. These patients stopped taking a hypnotic drug after transplantation. It might be difficult for a C–L psychiatrist to differentiate drug withdrawal delirium from delirium due to other causes if the previous psychiatric history isn't clearly clarified.19
Transplantation may create considerable psychological stress before and after the operation. Patients might encounter psychological problems related to transplantation.3,20,21 Delirium is the most frequently observed short-term psychiatric complication in patients undergoing liver transplantation, followed by adjustment disorders and affective disorders, which, in contrast, seem to have a good prognosis.2,22–24 As delirium is a disorder commonly encountered in post-transplantation cases, surgeons might have confidence in their management of these cases. In this study, 75% of all delirious cases were prescribed anxiolytic drugs before the psychiatric consultation. Although a C–L psychiatrist recommended antipsychotic drugs for six delirious patients, the surgeons' concordance with this recommendation was relatively low (33.3%). As the etiology of delirium could be multiple, the medication prescription was not necessarily the only factor in its recovery.19 In our study subjects with a delirious state, the improvement is likely to have come from judicious management of underlying physical problems and/or sedative drug withdrawal problems.
It might be difficult for the surgeon to differentiate ‘depressive disorders’ from ‘anxiety/dyssomnia disorders’, because four of the five depressive patients had insomnia/anxiety as their chief complaints and one case mainly complained of somatic discomforts. Some degree of anxiety symptoms frequently coexisted with depressive disorders. A C–L psychiatrist should be prudent in assessing symptoms of depression whenever a patient complains of anxiety and/or insomnia.
Consultees had 100% concordance with the recommendation of antidepressants in all depressive inpatients. All of these cases were prescribed with anxiolytics instead of antidepressants before psychiatric consultation. Their psychiatric conditions were much improved under the combination of antidepressant and anxiolytic prescriptions. Depressive symptoms can usually be eliminated or reduced to a tolerable level by brief supportive psychotherapy and psychotropic medication. Electroconvulsive therapy was also beneficial to one of our post-transplant inpatients, in the same way that a previous report by Showalter et al. described.25
Although insomnia is a common symptom and is often the best indicator for poor mental health, surgeons were less likely to prescribe hypnotics for dyssomnia than psychiatrists because of their concern for possible liver damage in these relatively stable patients. Three of the eight referral inpatients with ‘anxiety/dyssomnia disorder’ were given Lorazepam for dyssomnia following the C–L psychiatrist's recommendation. The reason for consultation among them was insomnia/anxiety. Lorazepam had frequently been used before psychiatric consultation because it is metabolized in the kidneys; is minimally affected by age; and is less sedative and less depressive to respiratory function than other benzodiazepines in patients with impaired oxidative metabolism.26
In summary, we have identified three main groups of psychiatric disorders among post-liver-transplant patients, namely, delirious state, depressive disorder, and anxiety/dyssomnia disorder. A C–L psychiatrist can quickly provide accurate psychiatric diagnosis and recommendations for effective management. This is particularly relevant in transplant patients because psychopharmacological treatment for them is quite complicated, and a C–L psychiatrist can assist a consultee in judicious management for psychiatric morbidity, especially depressive disorders.
We have found that the consultee's concordance with recommended drug prescriptions was high with antidepressants in depressive patients and low with antipsychotics in patients with delirium. Moreover, anxiolytics were frequently prescribed in post-transplant inpatients before psychiatric consultation.
The present study has several methodological limitations. First, the sample size is small and cannot represent the entire post-liver-transplant population. Hence, our findings may not be generalizable to all post-transplant patients. Second, the study is retrospective and conducted only in one medical center. Third, psychiatric diagnosis was made on a routine clinical assessment without the use of a standardized clinical interview. Four, there are some cases whose diagnoses are ambiguous because of the retrospective method employed in this study. Our future study will aim at a prospective follow up using a standardized clinical interview from the index consultation.