Serotonin syndrome in a case of depression with various somatic symptoms: the difficulty in differential diagnosis

A 65-year-old female patient with major depressive disorder suffered from clonus, shivering and impaired visual acuity after 20 mg/day of paroxetine administration. The symptoms were initially regarded as further manifestations of her somatic symptoms of depression, and paroxetine was increased to 30 mg/day resulting in frequent clonus, increased shivering, serious dysarthria, ongoing impairment in visual acuity and agitation. These symptoms subsided upon paroxetine discontinuation. Ten mg/day of paroxetine rechallenge provoked dysarthria, tremor and headache, but these symptoms improved again upon paroxetine discontinuation. These findings indicate that the patient's symptoms were not somatic in origin but were in fact the symptoms of serotonin syndrome. In conclusion, the present case suggests the difficulty in diagnosing serotonin syndrome in a patient with somatic symptoms.     

Hallucination induced by paroxetine discontinuation in patients with major depressive disorders

Discontinuation symptoms can follow the stoppage of almost all classes of antidepressants, including selective serotonin reuptake inhibitors. We report two cases suffering from visual and auditory hallucinations: Case 1 abruptly stopped taking paroxetine (20 mg/day), and Case 2 discontinued paroxetine after reducing the dose from 20 mg/day to 10 mg/day for 5 months. Both cases experienced visual and auditory hallucinations in addition to dizziness, headache, insomnia, and nausea a couple of days after paroxetine discontinuation. These observations suggest that hallucinations are a part of the discontinuation syndrome that results from paroxetine discontinuation. Physicians should be aware of this symptom.     

Case study: caudate glutamatergic changes with paroxetine persist after medication discontinuation in pediatric OCD

Proton magnetic resonance spectroscopy (1H-MRS) was used to examine glutamatergic (Glx) abnormalities in the caudate nucleus in pediatric obsessive-compulsive disorder (OCD), associated with severity of illness and response to acute (12 weeks) treatment with paroxetine. In this report, OCD symptoms improved markedly in an 8-year-old girl treated for 14 months with the selective serotonin reuptake inhibitor paroxetine (titrated from 10 to 40 mg/day). Paroxetine dose was then decreased in 10-mg decrements and discontinued without symptom recurrence. Serial 1H-MRS examinations were acquired before and after 12 weeks of paroxetine treatment (40 mg/day) and 3 months after medication discontinuation. A striking decrease in caudate Glx was observed after 12 weeks of treatment which persisted after medication discontinuation. These data provide further support for a reversible glutamatergically mediated dysfunction of the caudate nucleus in OCD that may serve as a pathophysiological and treatment response marker.     

Symptoms of delusion: the effects of discontinuation of low‐dose venlafaxine

Objective: We report a patient who experienced delusional symptoms during gradual discontinuation of low‐dose venlafaxine and required antipsychotic treatment. Method: Case report. Results: A 31‐year‐old woman with major depression had been treated abroad with venlafaxine before returning to Japan. Since venlafaxine is unavailable here, we supplemented her regular venlafaxine dosage of 37.5 mg/day with clomipramine 20 mg/day. After 5 weeks we reduced venlafaxine to 18.75 mg/day and uptitrated clomipramine to 40 mg/day. Four days later she developed delusions of reference, palpitations and nausea. Clomipramine was increased to 60 mg/day, and her symptoms subsided. Eight weeks later her supply of venlafaxine ran out, and within 4 days her condition deteriorated into more severe symptoms that required 4 months’ antipsychotic treatment. Conclusion: We speculate that her symptoms were discontinuation syndrome, including psychotic symptoms and physical symptoms, caused by (i) venlafaxine‐clomipramine interaction and/or (ii) the serotonin reuptake inhibitor‐like effects of low‐dose venlafaxine.     

Selective serotonin reuptake inhibitor discontinuation syndrome is associated with a rostral anterior cingulate choline metabolite decrease: a proton magnetic resonance spectroscopic imaging study.

The selective serotonin reuptake inhibitor (SSRI) discontinuation syndrome (DS) is an important potential complication of treatment for major depression. We hypothesized that SSRI treatment discontinuation, resulting in change in clinical state, would be associated with reduced rostral anterior cingulate choline (Cho) metabolite ratios.Individuals with a DSM-III-R diagnosis of unipolar major depression who had been stabilized on paroxetine (n = 13) or fluoxetine (n = 13) were study subjects. They were monitored for change in clinical state (mood ratings, discontinuation symptoms) and underwent proton magnetic resonance spectroscopic imaging of the rostral anterior cingulate 3 days after medication substitution with active SSRI and placebo.Placebo-day Cho/Cre (choline/total creatine) metabolite ratios were decreased in four paroxetine and two fluoxetine subjects meeting DS criteria, as compared with asymptomatic subjects (Mann-Whitney z = -2.31, p =.021).Discontinuation syndrome is associated with a rostral anterior cingulate Cho/Cre metabolite ratio decrease that may reflect dynamics of rostral anterior cingulate function.     

Neuroleptic Malignant Syndrome and Severe Thrombocytopenia: Case Report and Literature Review

We report an unusual case of thrombocytopenia associated with neuroleptic malignant syndrome (NMS). A 31-year-old Black male with a history of hypertension, partial seizures, and schizophrenia developed acute rigidity closely followed by severe hyperpyrexia (temperature 102°F), tachypnea, and tachycardia. His home medications at the time of presentation included propanolol 10 mg tid, haloperidol 10 mg bid, sodium valproate 500 mg bid, benztropine 1 mg bid, and haloperidol decanoate 100 mg i.m. every 3 weeks, from another psychiatric facility. Despite vigorous therapy for the hyperthermia, he rapidly developed significant hypoxia requiring mechanical ventilation. A diagnosis of neuroleptic malignant syndrome was made and the patient continued to receive aggressive supportive care. On hospital day 2 his platelet count dropped to 47,000/l and bottomed out at 36,000/l by day 3 with other blood cell counts remaining within normal limits. Over the next few days he showed rapid clinical improvement with normalization of his blood chemistries and he was discharged home after 5 days of hospitalization in good condition.     

Possible neuroleptic malignant syndrome related to concomitant treatment with paroxetine and alprazolam

A 74-year-old man with depressive symptoms was admitted to a psychiatric hospital due to insomnia, loss of appetite, exhaustion, and agitation. Medical treatment was initiated at a daily dose of 20 mg paroxetine and 1.2 mg alprazolam. On the 10th day of paroxetine and alprazolam treatment, the patient exhibited marked psychomotor retardation, disorientation, and severe muscle rigidity with tremors. The patient had a fever (38.2 degrees C), fluctuating blood pressure (between 165/90 and 130/70 mg mm Hg), and severe extrapyramidal symptoms. Laboratory tests showed an elevation of creatine phosphokinase (2218 IU/L), aspartate aminotransferase (134 IU/L), alanine aminotransferase (78 IU/L), and BUN (27.9 mg/ml) levels. The patient received bromocriptine and diazepam to treat his symptoms. 7 days later, the fever disappeared and the patient's serum CPK levels were normalized (175 IU/L). This patient presented with symptoms of neuroleptic malignant syndrome (NMS), thus demonstrating that NMS-like symptoms can occur after combined paroxetine and alprazolam treatment. The adverse drug reaction score obtained by the Naranjo algorithm was 6 in our case, indicating a probable relationship between the patient's NMS-like adverse symptoms and the combined treatment used in this case. The involvement of physiologic and environmental aspects specific to this patient was suspected. Several risk factors for NMS should be noted in elderly depressive patients whose symptoms often include dehydration, agitation, malnutrition, and exhaustion. Careful therapeutic intervention is necessary in cases involving elderly patients who suffer from depression.     

Paroxetine in human breast milk and nursing infants

OBJECTIVE: The purpose of this study was to determine the extent of infant medication exposure through breast-feeding during maternal treatment with paroxetine. METHOD: Breast milk and paired maternal and infant sera were collected after 10 days of maternal treatment with paroxetine at a stable daily dose (10-50 mg/day). All samples were analyzed by means of high-performance liquid chromatography with ultraviolet detection and a limit of detection of 2 ng/ml. RESULTS: Breast milk paroxetine concentrations were highly variable (2-101 ng/ml) and were present in all breast milk samples (N=108). A significant gradient effect was observed, with greater paroxetine concentrations found in later portions of breast milk (hind milk) than in early portions (fore milk). No clear time course of paroxetine excretion into breast milk was demonstrated, although maternal paroxetine daily dose reliably predicted both trough and peak breast milk concentrations over a 24-hour period. In 16 mother and infant serum pairs, no detectable concentrations of paroxetine were found in the serum of the nursing infants. CONCLUSIONS: This study extends previous data by demonstrating the presence of paroxetine in the breast milk of nursing women treated with this medication. The low concentrations of paroxetine in infant serum and lack of any observable adverse effects after maternal use of this medication while breast-feeding parallels the available data on other selective serotonin reuptake inhibitors.     

A case of Parkinson's disease with neuroleptic malignant syndrome induced by paroxetine]

We present a first case of Parkinson's disease with neuroleptic malignant syndrome by Paroxetine, one of the selective serotonin reuptake inhibitor (SSRI). The patient was a 73-year-old woman who had been diagnosed as Parkinson's disease for one and half year. The severity of her disease was categorized as Hoehn & Yahr 2nd degree and she had taken 0.25 mg/day of Pramipexole. Four days after the addition of 10 mg/day of Paroxetine for the treatment of her depression, she developed consciousness disturbance, severe muscular rigidity, tremor, fever, hyperhidrosis, incontinence and elevated serum creatine kinase level. According to diagnostic criteria, she was diagnosed as neuroleptic malignant syndrome probably induced by Paroxetine. Her clinical symptoms and laboratory data were improved seven days after intravenous drip infusion. We should recognize that SSRI could induce neuroleptic malignant syndrome in patients with Parkinson's disease.     

Case Report/Case Series: A Display of Hypomania in a Depressed Male in Response to Fluvoxamine

The present report describes the behavioural and psychological changes in a 55-year-old depressed male who displayed hypomania after the use of fluvoxamine in addition to other antidepressant medications. The patient experienced his first major depressive episode after the bankruptcy of his company. When fluvoxamine was prescribed at a dose of 50 mg/day in addition to sulphide at 150 mg/day and a 50 mg dose of trazodone before sleep seven months after admission, grinning and a violation of ward rules occurred repeatedly. The patient became verbally aggressive to the staff and addicted to gambling and alcohol. Six days after the cessation of fluvoxamine, his condition remitted. None of the neuromuscular abnormalities indicative of serotonin syndrome appeared during the episode. Upon review of previous reports on manic switches induced by SSRIs and other antidepressants, we speculate that the ftuvoxamine accounted for his hypomania.     

A display of hypomania in a depressed male in response to fluvoxamine.

The present report describes the behavioural and psychological changes in a 55-year-old depressed male who displayed hypomania after the use of fluvoxamine in addition to other antidepressant medications. The patient experienced his first major depressive episode after the bankruptcy of his company. When fluvoxamine was prescribed at a dose of 50 mg/day in addition to sulpiride at 150 mg/day and a 50 mg dose of trazodone before sleep seven months after admission, grinning and a violation of ward rules occurred repeatedly. The patient became verbally aggressive to the staff and addicted to gambling and alcohol. Six days after the cessation of fluvoxamine, his condition remitted. None of the neuromuscular abnormalities indicative of serotonin syndrome appeared during the episode. Upon review of previous reports on manic switches induced by SSRIs and other antidepressants, we speculate that the fluvoxamine accounted for his hypomania.     

Possible therapeutic effect of clonazepam upon elderly depressive patients

The patient, a 77‐year‐old man, was diagnosed with senile depression. He was also diagnosed with depression at other hospitals, and pharmacotherapy by antidepressants was carried out. He was given sulpiride, selective serotonin reuptake inhibitors, a serotonin‐norepinephrine reuptake inhibitor, an atypical antidepressant, and tricyclic and tetracyclic antidepressants, but conventional pharmacotherapies using these antidepressant drugs did not alleviate his symptoms. The patient was then administered 0.5 mg/day of clonazepam at bed time. Following 2 weeks of administration, his symptoms were alleviated. The dosage of clonazepam was increased to 0.75 mg/day and remission was facilitated. Four weeks later, the patient displayed further alleviation of his depressive symptoms, so he has been continued on 0.75 mg/day of clonazepam. Essential drug selections for senile depression includes selective serotonin reuptake inhibitors, serotonin‐norepinephrine reuptake inhibitors, and atypical antidepressants, but when these are ineffective, tricyclic antidepressants or tetracyclic antidepressants are alternatively selected. When a patient’s symptoms are not alleviated by essential drug selection, as occurred in the current case, clonazepam is considered to be another therapeutic candidate. If they fail to alleviate symptoms, however, then early referral to a specialist is crucial. Enhancing primary‐care physicians’ understanding of senile depression and coordination with specialists is essential in the medical care of elderly patients with depression.     

Purple glove syndrome caused by oral administration of phenytoin

A severely handicapped boy had been treated with phenytoin and his seizures were controlled well. At 10 years of age, a pharmacy gave about 1000 mg of phenytoin instead of the prescribed 100 mg of the drug per day. Several hours after the initial administration, the patient became drowsy and his hands and feet turned dark purple with marked swelling. Four days later, his mother stopped administering the phenytoin to him and took him to hospital. After fluid therapy was started, the swelling and discoloration of both his hands and feet improved gradually and disappeared 11 days after drug discontinuation. Purple glove syndrome is defined as the edema, discoloration, and pain occurring in the distal limb where intravenous phenytoin has been administered. This might be the first report of purple glove syndrome caused by the oral administration of a large quantity of phenytoin.     

A case report on elderly psychotic-like symptoms caused by antidepressant discontinuation

ObjectivesCure for severe depression in elderly patients with psychotic symptoms should consider not only the results of major depression but also the nature of antidepressants and their side effects. Psychiatric disability is higher in patients who have greater deterioration in neurological function.MethodsIn addition to reviewing antidepressant discontinuation syndrome and depressive disorder, this study describes an elderly woman with mild depression that developed into major depression, related to high suspicion of delirium, diagnosed based on patient history, physical health examination, neurological examinations, family history, and laboratory data, with subsequent treatment plan.ResultsThe treatment results and prognosis indicate that patients with paroxetine antidepressant deactivation may enable early use of low-dose quetiapine with less anticholinergic and extrapyramidal side effects for the treatment of depression in elderly patients with psychotic symptoms. The poor prognostic factors for patients were chronic environmental stress (poverty) and lack of a social support system. Although the patient lived with her children and grandchildren, she rarely received care. Hence, it was not possible to monitor her condition and medication intake.ConclusionsThe consensus is that the abrupt discontinuation of short half-life selective serotonin reuptake inhibitors (SSRIs), such as paroxetine can be associated with transient symptomatology, much of which is of a serotonergic nature. Psychotic-like symptoms have also been reported in both controlled trials and large patient databases.     

Serotonergic antidepressants and linezolid: a retrospective chart review and presentation of cases

OBJECTIVE: To report the results from a retrospective chart review looking at the combination of linezolid and serotonergic antidepressants and to report two cases of serotonin syndrome which were identified at our hospital. Case SUMMARY: During the retrospective chart review one case of serotonin syndrome was identified. A 65-year-old female was receiving escitalopram for the treatment of depression prior to admission. Linezolid therapy was initiated on admission and two days later the patient had a tonic-clonic seizure. Escitalopram was discontinued and the patient did not have any further seizure activity. In a second case, a 37-year-old male was receiving citalopram during hospitalization and was started on concomitant linezolid. The patient had myoclonus and was observed to be tremulous throughout therapy with linezolid. Ten days after discontinuation of linezolid the patient continued to have symptoms until the withdrawal of citalopram. The Naranjo probability scale scores the first case as possibly related and the second case as probably related to the combination. DISCUSSION: It has been well documented in the literature that the combination of linezolid and serotonergic antidepressants may cause serotonin syndrome. In this retrospective chart review only one patient of 53 (1.8%) had symptoms highly suggestive of serotonin syndrome. A second patient continued to have symptoms of serotonin syndrome even after withdrawal of linezolid. CONCLUSIONS: This retrospective review and subsequent case reports confirm the rare, but serious, potential of serotonin syndrome associated with the combination of linezolid and serotonergic antidepressants.     

Brain kinetics of paroxetine and fluoxetine on the third day of placebo substitution: a fluorine MRS study

OBJECTIVE: This study tested whether a relationship exists between concentration and response following discontinuation of selective serotonin reuptake inhibitors. METHOD: Eight patients with remitted major depression who were taking 20 mg/day of either fluoxetine or paroxetine underwent placebo substitution for 3 days. Serum drug and brain fluorine levels were obtained before and after placebo substitution. RESULTS: With placebo substitution, a mean of 88% (SD=13%) of brain fluorine signal from fluoxetine (plus fluorinated metabolites) remained, compared with a mean of 38% (SD=17%) of the brain fluorine signal from paroxetine (plus fluorinated metabolites). Among patients taking paroxetine, adverse events during placebo substitution correlated highly with steady-state brain drug levels. CONCLUSIONS: The correlation of clinical effects with brain drug levels in the paroxetine group suggests that relationships between drug response and brain drug concentrations merit further investigation.     

A randomized,double-blind,placebo-controlled study of the effects of adjunctive paroxetine in panic disorder patients unsuccessfully treated with cognitive-behavioral therapy alone

BACKGROUND: Both cognitive-behavioral therapy and treatment with selective serotonin reuptake inhibitors (SSRIs) have proved to be effective in the treatment of panic disorder. The present study examined the effects of paroxetine added to continued cognitive-behavioral therapy in patients who were unsuccessfully treated with initial cognitive-behavioral therapy alone. METHOD: 161 patients with panic disorder with or without agoraphobia (DSM-IV criteria) underwent a manual-guided cognitive-behavioral therapy of 15 sessions. Forty-three unsuccessfully treated patients from this group were included in a double-blind, placebo-controlled, next-step treatment study consisting of continued cognitive-behavioral therapy plus adjunctive paroxetine at a dose of 40 mg/day or continued cognitive-behavioral therapy plus placebo. RESULTS: Overall, patients in the cognitive-behavioral therapy plus paroxetine condition improved significantly on agoraphobic behavior (p < .05) and anxiety discomfort (p < .01), whereas patients in the cognitive-behavioral therapy plus placebo condition did not. Effect sizes in the cognitive-behavioral therapy plus paroxetine condition ranged from 1.0 to 1.8 and in the cognitive-behavioral therapy plus placebo condition, from 0.4 to 1.0. CONCLUSION: Patients with panic disorder who are unsuccessfully treated with initial cognitive-behavioral therapy may benefit from the addition of an SSRI as a second treatment modality. The importance of timely evaluation of treatment results is emphasized.     

Misdiagnosis of antidepressant discontinuation symptoms

OBJECTIVE: To demonstrate that when antidepressants are switched, discontinuation symptoms from the first antidepressant may be misdiagnosed as adverse effects of the second antidepressant. METHOD: Single case report. RESULTS: A female patient was switched from paroxetine to dothiepin due to lack of efficacy. Over the next week she developed physical symptoms which she and her doctor regarded as side effects of dothiepin. It was decided to change the dothiepin and a second opinion was obtained regarding a suitable alternative. At that point it was realized that her symptoms represented a paroxetine discontinuation syndrome. The patient was reassured and continued dothiepin. The discontinuation symptoms resolved over the next 3 weeks and her depression subsequently remitted. CONCLUSION: Increased professional awareness of discontinuation symptoms is necessary to prevent misdiagnosis and inappropriate treatment.     

Nine-month predictors and outcomes of SSRI antidepressant continuation in primary care

BACKGROUND: This study aimed to identify the predictors and outcomes of SSRI antidepressant continuation, discontinuation and switching over a 9-month period of naturalistic observation. METHODS: Primary care patients (n=573) with physician-diagnosed depression from 37 practices were randomized to an open-label trial of one of three selective serotonin reuptake inhibitors (SSRIs) managed in their primary care setting. Psychiatric characteristics and treatment course were assessed at baseline and at 1, 3, 6 and 9 months after medication initiation. RESULTS: Nineteen percent of patients switched SSRIs, which occurred significantly sooner than discontinuation (median: 41 vs.100 days). Time to discontinuation was primarily explained by baseline patient skepticism about taking an antidepressant (62% increase in discontinuation risk). In contrast, time to switch was associated with greater impairment at baseline and lesser improvement in impairment during the first month on medication. Patients who discontinued were significantly less likely to be depressed 9 months after starting medication than those who either continued or switched medication, and were less symptomatic and impaired than patients who switched. CONCLUSIONS: Baseline impairment may increase the risk for SSRI antidepressant switching. Additionally, patient skepticism about antidepressants predicts early SSRI discontinuation and may predict rapid recovery. Intent-to-treat analyses in nonrandomized clinical trials may paradoxically inflate antidepressant effect sizes.     

Tolerability of paroxetine in Parkinson's disease: a prospective study.

Depression is a common finding in patients with Parkinson's disease (PD). Traditionally, depression has been treated with tricyclic antidepressants, which are often associated with undesirable side effects that may limit their use in PD. Few studies have been performed with selective serotonin reuptake inhibitors (SSRIs) in these patients. We assessed the tolerability of the SSRI antidepressant paroxetine (10-20 mg once per day) in 65 outpatients with PD and depression for a period of at least 3 months. Treatment was continued for 125.3+/-89.6 days (mean +/- standard deviation) in 52 patients. In these subjects the Hamilton Disease Rating Scale improved from 21.7+/-6.4 to 13.8+/-5.8 (p <0.001). Overall, 13 patients stopped paroxetine after 9.6+/-10.6 days because of adverse reactions. Two patients reported increased "off" time and tremor that reversed after treatment was stopped. No risk factors for intolerance were identified. Paroxetine is a safe and effective drug to treat depression in PD.