Low-dose Mirtazapine Research Articles

A case of delirium following treatment with low dose mirtazapine and pregabalin

IntroductionPregabalin is a gamma-aminobutyric acid analogue used for the treatment of neuropathic pain, partial-onset-seizures, fibromyalgia, and anxiety disorders. Mirtazapine is an atypical antidepressant used in major depression and often prescribed off-label for insomnia. Delirium, an acute confusional state, is a very rare adverse reaction of both medications.ObjectivesWe report a case of an elderly patient treated with low dose pregabalin and mirtazapine who developed drug-induced delirium which resolved rapidly upon withdrawal of both drugsMethods A 75-year-old woman was admitted for symptoms of anxiety, various bodily complaints (dysphagia, headache, tinnitus, weakness) and sleep-onset insomnia over the preceding 2 months. On admission, examination revealed an apparently anxious, uneasy and emotional looking patient. Mini mental state examination, as well as clock drawing and copying were normal, suggesting absence of cognitive impairment. Physical examination was unrevealing except for high blood pressure recordings (150/90 mmHg). Laboratory testing indicated creatinine at 1.19 mg/dl, with a creatinine clearance moderately decreased at 38 ml/min. Upon admission, she was placed on pregabalin 25 mg bid and mirtazapine 30 mg ¼ tablet qd.ResultsThree days after admission, pregabalin was increased to 25 mg tid. On the same day and about 2 hours after the night dose, the patient acutely developed delirium: she presented confusion, disorientation, incoherence, restlessness and deterioration of her anxiety. On physical examination she was afebrile with no hypertonia or ataxia. An urgent brain magnetic resonance imaging was grossly unrevealing. Pregabalin and mirtazapine were discontinued, as a drug-induced delirium was suspected. She received as a symptomatic treatment lorazepam progressively up to 4 mg qd. Symptoms of delirium resolved rapidly, and she was discharged days later with full functional recoveryConclusionsCases of delirium have been described following treatment with pregabalin, but in significantly higher doses. Pregabalin relies heavily on renal clearance for its excretion and the dose should be adjusted in patients with creatine clearance below 60 ml/min. As our patient had a moderate decrease in renal clearance, we prescribed a dose within suggested limits, but in combination with mirtazapine led to the appearance of a drug-induced delirium. In conclusion, combined therapy with low-dose pregabalin and mirtazapine seems to account for the development of delirium in our patient as based on its temporal association with the initiation of this drug combination and its prompt resolution upon withdrawal of these two agentsDisclosure of InterestNone Declared

Effectiveness and adverse effects of the use of mirtazapine as compared to duloxetine for fibromyalgia: real-life data from a retrospective cohort.

On the background of a restricted armamentarium of drugs available for the management of fibromyalgia (FM), we aimed to compare the real-world effectiveness of two serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine (MTZ) and duloxetine (DLX) in FM. A medical records review was done to identify patients diagnosed with FM and prescribed a stable dose of either MTZ or DLX for more than 6months. Their present status was determined by a telephonic interview which included a subjective assessment of improvement (Likert scale), FIQR (Revised Fibromyalgia Impact Questionnaire), adverse drug effects and compliance. One-fifty-eight patients were screened to include 81 patients [mean age 46.7 (± 13.0) years, 64 (79%) females]. Sixty (79%) had primary fibromyalgia and 66 (81.5%) were on DLX (20-40mg) while 15(18.5%) were on MTZ (7.5mg). In addition to the drugs, lifestyle modification was followed by 57 (70.3%). A moderate-to-good improvement was seen in 66 (81.5%), while 15 (18.5%) reported poor to no improvement overall. In the DLX group, a majority (59, 89.4%) showed moderate-to-good improvement compared to 7(46.7%) on MTZ [p = 0.001, 9.6(2.6-34)]. However, FIQR was similar for those on DLX (3.6 ± 0.9) and MTZ (3.8 ± 0.7). Adverse effects were reported for 51 (77%) of patients on DLX and all (100%) on MTZ with a poorer compliance with MTZ 5 (33.3%) compared to DLX 47 (71.2%) [p = 0.008, OR 0.1(0.03-0.4)]. On multivariate analysis, DLX use [OR 16.7 (95% CI 2.7-100); p = 0.008] and lifestyle modification [p = 0.002; OR 11.2(1.5-83.3)] were associated with better subjective outcomes. Low-dose MTZ appears to be inferior to DLX in the management of FM in this real-world cohort.

Pathophysiology and management of Akathisia 70 years after the introduction of the chlorpromazine, the first antipsychotic.

Akathisia is among the most troubling effects of psychiatric drugs as it is associated with significant distress on behalf of the patients, and it limits treatment adherence. Though it most commonly presents during treatment with antipsychotic drugs which block dopamine D2 receptors, Akathisia has also been reported during treatment with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), stimulants, mirtazapine, tetrabenazine and other drugs. This article was designed as a narrative review on akathisia with a focus on its clinical presentation, pathophysiology and management. A PubMed search for akathisia was conducted which returned 8481 articles. Akathisia is experienced as severe restlessness commonly accompanied by dysphoria and purposeless movement which relieves subjective tension. It has been attributed to an imbalance between dopaminergic and noradrenergic neurotransmission in the basal ganglia. Acute akathisia commonly resolves upon treatment discontinuation but tardive and chronic akathisia may persist after the causative agent is withdrawn and prove resistant to pharmacological treatment. Even drugs which induce no other extrapyramidal side effects (such as clozapine, quetiapine, aripiprazole and cariprazine) may induce akathisia. A high index of suspicion should be maintained in patients with motor disabilities, drug-induced parkinsonism and those under mechanical restraint. Propranolol and low-dose mirtazapine are the most thoroughly studied pharmacological interventions for akathisia, though benzodiazepines, voltage-gated calcium channel blockers (gabapentin, pregabalin) and opioids may be effective. Pharmacological management may pose a challenge in chronic akathisia. Rotation between different pharmacological management strategies may be optimal in resistant cases. Discontinuation of the causative drug and use of b-blockers, mirtazapine, benzodiazepines or gabapentinoids for symptomatic relief is the basis of management.

Manage antipsychotic-induced akathisia by making changes to the antipsychotic drug regimen and/or adding anti-akathisia agents

Antipsychotic-induced akathisia (AIA) is a common and distressing adverse effect associated with many first- and second-generation antipsychotics. The risk of developing AIA can be minimized by administering the minimal effective dosage of an antipsychotic, avoiding rapid dose escalation and avoiding antipsychotic polypharmacy. Once AIA is diagnosed, patients should first receive an adjustment in their antipsychotic drug regimen (i.e. stop antipsychotic polypharmacy if applicable, lower the dosage of the antipsychotic medication or switch to an antipsychotic with lower AIA potential). If further intervention is needed, propranolol is considered as the first-choice anti-akathisia agent. Alternatively, low-dose mirtazapine, anticholinergics and benzodiazepines can also be considered.

Treatment of Antipsychotic-Induced Akathisia: Role of Serotonin 5-HT2a Receptor Antagonists

Akathisia is one of the most prevalent and distressing adverse effects associated with antipsychotic drug treatment. Propranolol, a non-selective beta-adrenergic receptor antagonist, is currently considered a first-line treatment for antipsychotic-induced akathisia (AIA). Surprisingly, the evidence for its anti-akathisia effect is modest. Propranolol's side effects (e.g. orthostatic hypotension, bradycardia), contraindications (e.g. asthma) and increased complexity in titration schedules limit its use in some patients. Anticholinergic agents and benzodiazepines merely provide symptomatic relief in patients with AIA. Effective and well-tolerated treatment remains a major unmet need in akathisia and warrants a search for new anti-akathisia agents. Accumulating evidence during the last two decades indicates that agents with marked postsynaptic serotonin 5-HT2a receptor antagonism (ritanserin, cyproheptadine, trazodone, mianserin, mirtazapine) may represent a new class of potential anti-akathisia remedies. Among these agents, low-dose mirtazapine (7.5mg or 15mg once daily) has demonstrated the most compelling evidence for therapeutic efficacy. In this narrative review we highlight the clinical significance of AIA, outline major approaches for its management and propose a practical algorithm for its treatment.

A double-blind randomized placebo-controlled study of low dose mirtazapine once daily in patients of major depressive disorders on escitalopram

Background: The SSRIs being used as 1st line therapy in treatment of depression have delayed therapeutic effect which makes the patient vulnerable to an increased risk of suicide and decreased adherence to the treatment and will prematurely discontinue the therapy. The present study was conducted to evaluate if low dose mirtazapine-escitalopram combination therapy has any add on benefit over monotherapy with escitalopram.Methods: In a single-centered, comparative study involving patients with depression attending the out-patient after screening and exclusion, 60 eligible patients were randomly assigned to receive tablet mirtazapine 7.5 mg plus tablet escitalopram 10 mg intervention or tablet escitalopram 10 mg plus placebo intervention in a double-blind 6-week treatment phase. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS) and Montgomery-Asberg Depression Rating Scale (MADRS) score from baseline. Participants were evaluated at baseline, 1st, 2nd,4th and 6th week. Results were analyzed using Chi-Square test for adverse effects and independent t-test analysis for efficacy parameter.Results: In the analysis of results at 6th week the numbers of patients achieved remission in mirtazapine group are more with a p-value of 0.018 which is significant and the numbers of responders in mirtazapine group are also more which is statistically significant on chi-square test. There is no significant difference was observed between the two groups with reference to occurrence of adverse effect.Conclusions: Adding low dose mirtazapine has an added benefit in terms of efficacy and getting remission early with more number of responders in the treatment of major depression.

Very Low-Dose Mirtazapine (7.5 mg) in Treatment of Acute Antipsychotic-Associated Akathisia.

Some evidence suggests that off-label use of mirtazapine (15 mg) is effective in treatment of acute antipsychotic-associated akathisia (AAA). We analyzed whether a lower dose of mirtazapine (7.5 mg) maintained its antiakathisia properties while exhibiting better tolerability in patients with schizophrenia and mood disorders who developed acute AAA. Medical charts were retrospectively evaluated for 12 patients with AAA. All scored at least 2 (mild akathisia) on the Barnes Akathisia Rating Scale (BARS) and were treated with mirtazapine (7.5 mg) for a mean of 10.3 days. There was a statistically significant decrease in the BARS subjective, distress, and global (P < 0.01 to P < 0.001), but not objective (P = 0.63), subscales. Five participants (41.6%) fulfilled the predefined criterion of response, a decrease of at least 2 points on the BARS global subscale. The positive antiakathisia effect of mirtazapine was observed predominantly in aripiprazole-treated patients. Mirtazapine (7.5 mg) was well tolerated, and no clinically significant adverse effects, primarily drowsiness or increased appetite, were reported. A large-scale controlled evaluation is warranted to substantiate clinical utility of off-label use of mirtazapine (7.5 mg) for patients with AAA.

Short-Term Safety of Paroxetine Plus Low-Dose Mirtazapine During Lactation.

Selective serotonin reuptake inhibitors (SSRIs), especially sertraline and paroxetine, are first-line antidepressants in the treatment of postpartum depression in breastfeeding women as these drugs are well tolerated by most breastfed infants. Although some women with these diagnoses require additional antidepressants to SSRIs, the safety of combined usage of SSRIs and mirtazapine is currently unknown. This report includes short-term safety data of breastfed infants exposed to paroxetine plus low-dose mirtazapine.

Treatment of Antipsychotic-Related Akathisia Revisited: The Role of Serotonin 2A Receptor Antagonists.

Akathisia remains a prevalent, clinically significant, and therapeutically challenging adverse event associated with antipsychotic treatment. Compelling evidence supports therapeutic efficacy and clinical utility of agents with marked serotonin 2A receptor antagonism, primarily low-dose mirtazapine, as an effective and well-tolerated antiakathisia treatment.

Beneficial effect of low-dose mirtazapine in acute aripiprazole-induced akathisia

Low-dose mirtazapine was found to be efficacious for neuroleptic-induced akathisia. We evaluated whether mirtazapine is also effective for akathisia induced by the partial dopamine D2 receptor agonist aripiprazole. Medical charts were retrospectively analyzed for eight patients who developed akathisia while being treated with aripiprazole. All scored at least 2 (mild akathisia) on the Barnes Akathisia Rating Scale (BARS) and were treated with mirtazapine (15 mg/day) for a mean of 8.5 days. There was a statistically significant reduction in the BARS subjective, distress, and global (P<0.01 to P<0.001), but not objective (P=0.21) subscales. Five (62.5%) patients fulfilled the criteria of response, a decrease of at least two points on the BARS global subscale. Low-dose mirtazapine was well tolerated, and mild sedation, the only side effect (three patients), was transient. A large-scale controlled investigation is warranted to substantiate clinical utility of mirtazapine for akathisia induced by aripiprazole and other second-generation antipsychotics.

Effects of low‐dose mirtazapine on driving performance in healthy volunteers

This study aimed to assess whether a lower initial dose of mirtazapine can lessen the harmful effect on driving performance or not in a double-blinded, placebo-controlled crossover trial. Thirteen healthy men received 8 days of continuous nocturnal doses of mirtazapine at 7.5 mg or 15 mg, or placebo. At baseline and on days 2 and 9, subjects performed three driving tasks (road-tracking, car-following, and harsh-braking tasks) using a driving simulator and a Continuous Performance Test. Stanford Sleepiness Scale (SSS) scores were also assessed. In the mirtazapine 7.5 mg series, 15 mg of mirtazapine was additionally administered on day 9, followed by all the same assessments on day 10. Mirtazapine 7.5 mg had no significant effects on any tasks except for SSS compared with placebo. Mirtazapine 15 mg impaired road-tracking task and SSS. The increase in mirtazapine dose also had no significant effects on any tasks compared with those before dose increase. Mirtazapine 7.5 mg did not cause driving impairment compared with mirtazapine 15 mg, while both doses of mirtazapine produced subjective somnolence. The increase in mirtazapine had no detrimental effects on psychomotor performance. Initial low-dose mirtazapine may be safer for automobile driving than the normal starting dose.

Low-dose mirtazapine added to selective serotonin reuptake inhibitors in pregnant women with major depression or panic disorder including symptoms of severe nausea, insomnia and decreased appetite: three cases

Data on the use of a combination of antidepressants during pregnancy are inadequate. This report presents the beneficial effect of low-dose mirtazapine added onto selective serotonin reuptake inhibitors in the treatment of the symptoms of severe nausea, insomnia and loss of appetite accompanying psychiatric disorders during pregnancy, which is an important problem in clinical practice. The psychiatric diagnoses were determined with the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Assessments were performed with the Clinical Global Impression-Improvement Scale and the 17-item Hamilton Rating Scale for Depression. Further studies should be carried out to confirm the positive effects and safety of an additional low-dose mirtazapine in these cases.

Efficacy and safety of add on low-dose mirtazapine in depression

Objectives:Although antidepressant medications are effective, they have a delayed onset of effect. Mirtazapine, an atypical antidepressant is an important option for add-on therapy in major depression. There is insufficient data on mirtazapine in Indian population; hence this study was designed to study the add-on effect of low-dose mirtazapine with selective serotonin reuptake inhibitors (SSRIs) in major depressive disorder (MDD) in Indian population.Materials and Methods:In an open, randomized study, 60 patients were divided into two groups. In Group A (n=30) patients received conventional SSRIs for 6 weeks. In Group B (n=30) patients received conventional SSRIs with low-dose mirtazapine for 6 weeks. Patients were evaluated at baseline and then at 1, 2, 3, 4, 5, and 6 weeks.Results:There was significant improvement in Hamilton Depression Rating Scale (HDRS), Montgomery and Asberg depression rating scale (MADRS) scores (P<0.05) in both groups. Mirtazapine in low dose as add on therapy showed improvement in scores, had earlier onset of action, and more number of responders and remitters as compared to conventional treatment (P<0.05). No serious adverse event was reported in either of the groups.Conclusion:Low-dose mirtazapine as add-on therapy has shown better efficacy, earlier onset of action and more number of responders and remitters as compared to conventional treatment in MDD in Indian patients.

A case of discontinuation syndrome following the discontinuation of low-dose mirtazapine therapy in malignant lymphoma

We report the case of a 69-year-old woman with malignant lymphoma who suffered from major depressive disorder. A low dose of mirtazapine (15 mg/day) brought about dramatic improvement in her mental status. However, after discontinuation of the mirtazapine, anxiety, restlessness, irritability, nausea, insomnia, imbalance and sensory disturbances occurred. When mirtazapine therapy was restarted, these symptoms resolved completely. These findings suggest that discontinuing even a low dose of mirtazapine might result in discontinuation syndrome, particularly in patients in poor physical condition. To the best of our knowledge, this is the first report describing a discontinuation syndrome due to the discontinuation of a low dose of mirtazapine.

Mirtazapine Augmentation for Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction: A Retropective Investigation

The aim of the present study was to retrospectively identify sexual dysfunction changes in the patients under mirtazapine-augmented serotonin reuptake inhibito (SSRI) treatment. The study comprised medical records of 20 outpatients, under mirtazapine-augmented SSRI treatment for their major depressive disorder, who had been selected among the patients that had developed sexual dysfunction to previous treatment as monotherapy, with SSRI for at least six weeks. These drugs were maintained and mirtazapine were added (15-45 mg/day). There was a significant difference in scores between baseline and week 4 or week 8 on the both Hamilton Depression Rating and Arizona Sexual Experience Scale. According to Clinical Global Impression-Improvement, 68.4% of the patients were responders. The use of low-dose mirtazapine as an add-on treatment to SSRIs appears to be an effective and well-tolerated augmenttaion for sexual dysfunction caused by SSRIs.

Mirtazapine-Associated Urinary Retention

Back to table of contents Previous article Next article LETTERFull AccessMirtazapine-Associated Urinary RetentionPanagiotis Oulis M.D., Ph.D.,Athanasios Leonardos M.D.,George C. Koulouris M.D.George Konstantakopoulos M.D.,Panagiotis Oulis M.D., Ph.D.Search for more papers by this author,Athanasios Leonardos M.D.Search for more papers by this author,George C. Koulouris M.D.Search for more papers by this authorGeorge Konstantakopoulos M.D.Search for more papers by this author,Published Online:1 Jul 2010https://doi.org/10.1176/jnp.2010.22.3.352.e21AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: Mirtazapine, an efficacious antidepressant of dual noradrenergic and serotoninergic mechanisms of action, is deemed particularly safe and well tolerated, especially with respect to its urinary side effects, owing to its very weak muscarinic anticholinergic properties. 1 Moreover, it has been found to ameliorate l -dopa-induced dyskinesias in patients with Parkinson’s disease. 2 Its safety in this respect makes it an attractive choice for the treatment of depression in elderly male patients with normal age-related prostate hypertrophy and concomitant Parkinson’s disease, whereby the possibility of incomplete voiding cannot be excluded. 3 To the best of our knowledge there are as yet no available reports on mirtazapine’s potential to induce urinary retention in this patient population. In the following we report on such a case, whereby the administration of low-dose mirtazapine resulted in the patient’s urinary retention. Case Report This is the case of an 85-year-old man with asymptomatic age-related benign prostate hypertrophy since the age of 77 and a 3-year history of Parkinson’s disease, for which he underwent a treatment with a compound of l -dopa, carbidopa, and entacapone at the dosage of 200/50/800 mg/day, respectively, equally divided in four doses. Moreover, for the last few months, the patient exhibited symptoms of a major depressive episode of mild severity according to DSM-IV diagnostic criteria, for which he had been prescribed mirtazapine, 15 mg/day. However, within 24 hours after mirtazapine’s initiation, he suffered from acute urinary retention necessitating the insertion of a Foley catheter. Mirtazapine was immediately discontinued, and his urinary retention subsided within 24 hours. The same pattern reemerged upon a second trial of mirtazapine a week later. Afterward, the patient was prescribed citalopram, 20 mg/day, without any urinary side effects. In the course of the following year, his previously mentioned antiparkinsonian medication was progressively increased to 400/100/800 mg/day without recurrence of urinary retention. DiscussionAlthough urinary retention may occur spontaneously in patients with benign prostate hypertrophy, the repeated pattern of its conditional dependence on mirtazapine administration renders this hypothesis in our case highly unlikely. With respect to the mechanisms of mirtazapine-induced urinary retention, we should note that descending norepinephrine and 5-hydroxy-tryptamine (5-HT) pathways from the brain to the ventral horn of the sacral spinal cord, in the presence of the neurotransmitter glutamate, enhance pudendal nerve activity and thus increase smooth urethral sphincter muscle contraction. 4 Moreover, stronger norepinephrine than 5-HT reuptake inhibition may induce increased peripheral stimulation of norepinephrine receptors in the smooth urethral muscle, causing urinary hesitancy or even retention. On this score, we should be reminded of reboxetine’s—a selective norepinephrine reuptake inhibitor—potential to induce urinary hesitancy or even retention. 5 Therefore, although rare, urinary retention is a possible adverse event of antidepressant treatment with mirtazapine. Accordingly, clinicians should be aware of mirtazapine’s potential to induce urinary retention, especially in elderly male patients with asymptomatic age-related benign prostate hypertrophy. 1st Department of Psychiatry, Athens University Medical School, Eginition Hospital, Athens, GreeceUnit of Functional and Stereotactic Neurosurgery, Athens University Medical School, Department of Neurosurgery, Evangelismos Hospital, Athens, Greece1st Department of Psychiatry, Athens University Medical School, Eginition Hospital, Athens, Greece

Combination of low‐dose mirtazapine and ibuprofen for prophylaxis of chronic tension‐type headache

Chronic headaches are difficult to treat and represent the biggest challenge in headache centres. Mirtazapine has a prophylactic and ibuprofen an acute effect in tension-type headache. Combination therapy may increase efficacy and lower side effects. We aimed to evaluate the prophylactic effect of a combination of low-dose mirtazapine and ibuprofen in chronic tension-type headache. Ninety-three patients were included in the double-blind, placebo-controlled, parallel trial. Following a 4-week run-in period they were randomized to four groups for treatment with a combination of mirtazapine 4.5 mg and ibuprofen 400 mg, placebo, mirtazapine 4.5 mg or ibuprofen 400 mg daily for 8 weeks. Eighty-four patients completed the study. The primary efficacy parameter, change in area under the headache curve from run-in to the last 4 weeks of treatment, did not differ between combination therapy (190) and placebo (219), P = 0.85. Explanatory analyses revealed worsening of headache already in the third week of treatment with ibuprofen alone. In conclusion, the combination of low-dose mirtazapine and ibuprofen is not effective for the treatment of chronic tension-type headache. Moreover, the study suggests that daily intake of ibuprofen worsens headache already after few weeks in chronic tension-type headache.

Low-dose mirtazapine may be successful treatment option for severe nausea and vomiting

The antagonism of 5-HT3 receptor by mirtazapine results in an antiemetic effect, suggesting that mirtazapine could be considered a successful antiemetic agent in patients suffering from severe nausea and vomiting. There have been several reports of successful mirtazapine treatment for nausea or vomiting from secondary causes but cases of primary severe nausea and vomiting are still lacking, in particular, there are no reported cases in Asians. The authors report two cases with severe nausea and vomiting that were dramatically treated with mirtazapine in the Korean population.

Low-Dose Mirtazapine: A New Option in the Treatment of Antipsychotic-Induced Akathisia. A Randomized, Double-Blind, Placebo- and Propranolol-Controlled Trial

Preliminary evidence indicates a beneficial effect of serotonin 2A (5-HT(2A)) receptor antagonists in antipsychotic-induced akathisia (AIA). We investigated the antiakathisia effect, safety, and tolerability of low-dose mirtazapine, an agent with marked 5-HT(2A) antagonism. In a 7-day double-blind trial, 90 antipsychotic-treated patients meeting DSM-IV criteria for AIA were randomly assigned to mirtazapine (n = 30; 15 mg), propranolol (n = 30; 80 mg), or placebo (n = 30). Primary outcome measures were between-group differences in Barnes Akathisia Scale (BAS) global scores and in the proportion of responders (reduction of > or = 2 points on BAS). Analysis was by intention to treat. Twenty-four patients (26.6%) who were assigned treatment did not complete the study (7 mirtazapine, 8 propranolol, 9 placebo), due to lack of response (n = 19) and adverse events (n = 5). Both mirtazapine and propranolol significantly reduced AIA severity (BAS: -34% mirtazapine and -29% propranolol vs. placebo -11%; p = .012 and p = .023, respectively). Thirteen (43.3%) mirtazapine and 9 (30.0%) propranolol-treated patients versus 2 (6.7%) placebo-treated patients responded (the corresponding odds ratios 10.7 [95% confidence interval (CI), 2.1-53.3] and 6.0 [95% CI, 1.1-30.7]). Five (16.7%) of 30 propranolol-treated patients and none in the mirtazapine and placebo groups (p = .0195 for both) prematurely discontinued the study due to clinically significant hypotension or bradycardia. The comparable efficacy and better tolerability of low-dose mirtazapine versus propranolol, the current first-line treatment for AIA, position mirtazapine as a favorable candidate for the treatment of acute AIA and may improve current therapeutic practices.

Mirtazapine Treatment for Pathological Laughing and Crying After Stroke

Selective serotonin reuptake inhibitors (SSRIs) have been recognized as the treatment of choice for pathological laughing and crying (PLC), which is a common, distressing condition that follows stroke. There have been few reports about other treatment options for PLC. Here, the authors report rapid responses to mirtazapine in two patients with poststroke PLC who failed to respond to SSRIs or bupropion. In the first case, a 63-year-old woman with severe long-standing crying spells that had persisted for 3 months responded well to low-dose mirtazapine within a few days; she could not tolerate citalopram or sertraline. In the second case, both the laughing and crying spells of a 64-year-old woman were improved within a few days of mirtazapine administration, after they had not responded to bupropion. This is one of the first reports to suggest that mirtazapine may be an alternative to SSRIs for treating poststroke PLC.