Prophylactic Management of Women With Bipolar Disorder During Pregnancy and the Perinatal Period: Clinical Scenario-Based Practical Recommendations From A Group of Perinatal Psychiatry Authors.

ABSTRACT: Many women with bipolar disorder experience episodes of illness or relapses over the perinatal period, especially in the immediate postpartum period. Risks associated with treated/untreated psychopathologies and fetal exposure to bipolar medications make the management of bipolar disorder during these periods challenging for clinicians and patients. In light of the available effectiveness and reproductive safety data, the current clinical update based on the opinions of a group of international perinatal psychiatry authors recommends general considerations and specific management strategies for each possible clinical scenario, including mixed features, predominant polarity, diagnosis of subtypes of bipolar disorder, severity of previous episodes, and risk of recurrence of mood episodes.

A New Safety Scoring System for the Use of Psychotropic Drugs During Lactation.

BACKGROUND: Psychotropic drugs are frequently used to treat postpartum women with psychiatric diagnoses, especially psychotic disorder, major depression, and bipolar mood episodes. Pharmacotherapy in breastfeeding mothers is a major challenge. STUDY QUESTION: This article presents a new safety scoring system for the use of psychotropic drugs during lactation. STUDY DESIGN: The scoring system is based on the following 6 safety parameters: reported total sample, reported maximum relative infant dose, reported sample size for relative infant dose, infant plasma drug levels, prevalence of reported any adverse effect, and reported serious adverse effects. The total score ranges from 0 to 10. Higher scores represent a higher safety profile. RESULTS: According to this scoring system, sertraline and paroxetine, respectively, had the highest scores representing "very good safety profile." Citalopram, olanzapine, and midazolam were assigned to "good safety profile." Among drugs evaluated in this article, trifluoperazine, aripiprazole, amisulpride, clozapine, doxepin, zaleplon, and zolpidem are not recommended owing to safety scores ≤3. CONCLUSIONS: Most psychotropic drugs examined in this article have "moderate" or "low" safety profile.

Citalopram in Treatment of Pregnant Women With Panic Disorder: A Retrospective Study.

PURPOSE: The study aimed to investigate efficacy of citalopram in pregnant women with panic disorder. METHODS: The study data with 22 patients were retrospectively collected from clinical registers. The study was conducted in patients with and without comorbid major depression. The patients were evaluated using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, the Clinical Global Impression-Improvement Scale, the Hamilton Depression Rating Scale, and the Hamilton Rating Scale for Anxiety. FINDINGS: The Hamilton Depression Rating Scale and the Hamilton Rating Scale for Anxiety scores were significantly reduced after treatment with citalopram at 20 mg/d for 8 weeks. The response rate based on Clinical Global Impression-Improvement Scale was 68.2%. Patients with comorbid major depression seemed to have a lower response rate compared with nondepressed patients. IMPLICATIONS: The current study suggests that citalopram may be beneficial for in pregnant women with panic disorder.

The Use of Antidepressant Medications During Pregnancy and the Risk of Neonatal Seizures: A Systematic Review.

PURPOSE: This review examined the current literature about the potential relationship between the use of antidepressants during pregnancy and neonatal seizures. METHODS: PubMed was searched for English language reports published between January 1, 1996, and October 31, 2018, by using combinations of the following key words: pregnancy, neonatal outcome, neonatal convulsion, neonatal seizure, SSRI, selective serotonin norepinephrine reuptake inhibitor (SNRI), tricyclic antidepressant (TCA), antidepressants, sertraline, fluoxetine, paroxetine, citalopram, escitalopram, fluvoxamine, venlafaxine, mirtazapine, duloxetine, bupropion, amitriptyline, imipramine, and clomipramine. FINDINGS: A total of 9 relevant studies that met the review criteria were examined. The prevalence rates of neonatal seizures in the antidepressant groups and control groups were 0.30% to 0.91% and 0.10% to 0.30%, respectively. The use of selective serotonin reuptake inhibitors was associated with up to 5-fold increase in the risk of neonatal seizures. Compared with the controls, higher risks were reported in newborns of pregnant women using any antidepressant or tricyclic antidepressants albeit in a limited number of studies. Exposure to antidepressants in the third trimester of pregnancy appeared to be associated more with neonatal seizures compared with earlier exposure. IMPLICATONS: Although an increased risk of neonatal seizures in newborns antenatally exposed to antidepressants especially selective serotonin reuptake inhibitors may be suggested, the available studies have severe methodological limitations to enable any firm conclusion.

Antipsychotic Use During Pregnancy and the Risk of Gestational Diabetes Mellitus: A Systematic Review.

PURPOSE: This study aimed to review the current literature examining a potential relationship between the use of antipsychotic drugs during pregnancy and gestational diabetes mellitus (GDM). METHODS: PubMed was searched for English language reports between January 1, 1996, and March 31, 2018, by using combinations of the following key words: antipsychotics, pregnancy, FGAs, SGAs, GDM, obstetric outcomes, pregnancy outcomes, obstetric complications, maternal complications, clozapine, olanzapine, risperidone, aripiprazole, amisulpirde, ziprasidone, quetiapine, haloperidol, chlorpromazine, zuclopenthixol, and flupenthixol. Studies but not case reports, case series, or reviews published in a peer-reviewed journal were eligible for inclusion. RESULTS: A total of 10 relevant studies that met the review criteria were examined. Data from these studies indicated that the prevalence rates of GDM in pregnant women using antipsychotic drugs and the nomedication group were 2.6% to 22% and 0.95% to 10.7%, respectively. Most comparative studies reported that antipsychotic treatment during pregnancy was not significantly associated with increased in risk of GDM. In addition, the study results also suggested that underlying maternal psychopathologies might affect the risk of GDM. IMPLICATIONS: Findings from some studies suggesting a higher risk of GDM in pregnant women who were administered antipsychotic drugs were not confirmed by results of many other studies. The current evidence suggests no significant relationship between antipsychotic drugs, including second- and first-generation antipsychotics, and the risk of GDM.

Maternal Antidepressant Use During Pregnancy and the Risk of Attention-Deficit/Hyperactivity Disorder in Children: A Systematic Review of the Current Literature.

PURPOSE: This study reviewed the current literature examining the potential relationship between use of antidepressants during pregnancy and attention-deficit/hyperactivity disorder (ADHD) in children. METHODS: PubMed was searched for English language reports between January 1, 1995, and July 31, 2017, by using combinations of the key words pregnancy, antidepressants, selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), children, offspring, and ADHD. Studies that reported association between ADHD in children and use of antidepressant in pregnant women were included in the review. RESULTS: A total of 7 relevant studies that met the review criteria were examined. The studies reported that compared with nonusers adjusted risks of ADHD in children were 1.2 to 1.6 for the use of any antidepressant, 0.91 to 1.66 for selective serotonin reuptake inhibitors, 1.1 to 1.4 for selective serotonin-norepinephrine reuptake inhibitors, and 1.1 to 1.8 for tricyclic antidepressants. There was some scientific evidences suggesting a connection between antidepressant use during all trimesters of pregnancy and increased risk of ADHD in children. In addition, the study results suggest that underlying maternal anxiety or depressive disorders may also contribute to increased risk of ADHD. IMPLICATIONS: Although some studies have suggested a moderately increased risk of ADHD in children with maternal antidepressant use during pregnancy, based on limitations and results of the studies, this review concluded that there is no strong evidence to suggest a causal link.

Neonatal outcomes in pregnant women with untreated and treated panic disorder.

OBJECTIVE: The objective of the present study was to compare neonatal outcomes including gestational age, birth weight and hospitalization of newborns of pregnant women with treated with antidepressants and untreated panic disorder. METHODS: The study sample included 146 pregnant women (44 patients with panic disorder treated with antidepressants, 52 patients with untreated panic disorder, and 50 healthy controls). Panic disorder was diagnosed by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: The highest proportions of preterm birth (28.8%), low birth weight (34.6%) and requirement of neonatal care (25.0%) were observed in infants of untreated patients. Pharmacotherapy group and control subjects had similar neonatal outcomes. Compared with infants of healthy subjects and the pharmacotherapy group, infants of untreated patients had significantly lower birth weight and gestational age at delivery. In addition, newborns of untreated patients had higher rate of hospitalization at the neonatal care unit. CONCLUSION: Our results suggest that treatment with pharmacotherapy of panic disorder during pregnancy may have beneficial effects on the risk of negative neonatal outcomes due to maternal panic disorder in the infants.

Is There Any Association Between Use of Antidepressants and Preeclampsia or Gestational Hypertension?: A Systematic Review of Current Studies.

OBJECTIVE: Hypertension in pregnant women is an important medical problem, which can cause morbidity and mortality in the fetus. This study reviewed the current literature examining the potential relationship between use of antidepressants during pregnancy and preeclampsia or gestational hypertension. METHODS: PubMed was searched for English-language reports between January 1, 1995, and December 31, 2015, by using combinations of key words pregnancy, pregnancy complications, preeclampsia, gestational hypertension, and antidepressants. Studies that reported the diagnosis of preeclampsia or gestational hypertension and use of antidepressant were included in the review. RESULTS: A total of 7 relevant studies that met the review criteria were examined. The studies reported that compared with nonusers adjusted relative risk of preeclampsia or gestational hypertension in antidepressant users was 1.28 to 1.53 for any antidepressant, 1.05 to 3.16 for selective serotonin reuptake inhibitors, 1.49 to 1.95 for selective serotonin-norepinephrine reuptake inhibitors, and 0.35 to 3.23 for tricyclic antidepressants. Consistently, antidepressant use during the second trimester of pregnancy was associated with increased risk of preeclampsia or gestational hypertension. However, possible contribution of severity, type, and comorbidity of underlying anxiety or depressive disorders is unclear in the current studies. CONCLUSIONS: Although some studies have suggested a moderately increased risk in pregnancy-specific hypertensive disorders with antidepressant treatment, the current data do not allow a definitive conclusion on this topic, because the studies have many methodological limitations. In addition, the effects of untreated depression or anxiety disorders cannot be disentangled from the results.

Delirium in patients with acute ischemic stroke admitted to the non-intensive stroke unit: Incidence and association between clinical features and inflammatory markers.

BACKGROUND: Stroke patients with development of delirium have unfavorable outcomes, higher mortality, longer hospitalizations, and a greater degree of dependence after discharge. Studies suggest that delirium is associated with abnormal immunological responses and a resultant increase in inflammatory markers. OBJECTIVE: Our aim was to determine whether there is an entity relationship between delirium, inflammation and acute ischemic stroke (AIS). METHODS: Sixty AIS patients admitted to the hospital were consecutively recruited. Delirium was diagnosed with the clinical assessment according to the Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum levels of Interleukin-1 beta (IL-1 beta), Interleukin 18 (IL-18), Tumor Necrosis Factor-alpha (TNF-alpha), Brain-Derived Neurotrophic Factor (BDNF), and Neuron Specific Enolase (NSE) at admission. RESULTS: Eleven (18.3%) of 60 patients were diagnosed with delirium, and the majority (n=8, 72.7%) was the hypoactive type. Delirious and non-delirious patients had similar demographic and clinical features. Delirious patients had significantly higher lengths of hospital stay, National Institutes of Health Stroke Scale (NIHSS) at admission and discharge compared to non-delirious patients. In addition, there was no significant statistical difference between delirious and non-delirious patients with AIS in respect of levels of TNF-alpha, IL-1 beta, IL-18, BDNF and NSE. This study suggests that delirium is not scarce in patients with AIS admitted to the non-intensive stroke unit, and that delirium developing after AIS seems not to be associated with serum TNF-alpha, IL-1 beta, IL-18, BDNF and NSE but is associated with length of hospital stay and stroke severity.

Second-Generation Antipsychotics During the Lactation Period: A Comparative Systematic Review on Infant Safety.

OBJECTIVE: This review examined the safety of second-generation antipsychotics (SGAs) in exposed breastfed infants. METHODS: PubMed was searched for English language reports between January 1, 1990, to June 30, 2015, by using combinations of the key words breastfeeding, lactation, postpartum period, puerperium, antipsychotics, second-generation antipsychotics, olanzapine, quetiapine, risperidone, ziprasidone, aripiprazole, amisulpride, clozapine, asenapine, lurasidone, and iloperidone. Case reports, case series, and prospective or cross-sectional studies including relevant data such as relative infant dose (RID), milk-to-plasma ratio (M/P ratio), infant drug plasma levels, and adverse events were identified. RESULTS: A total of 37 relevant reports were examined. These reports included a total of 206 infants exposed to olanzapine (n = 170), quetiapine (n = 14), risperidone/paliperidone (n = 8), clozapine (n = 6), aripiprazole (n = 4), ziprasidone (n = 2), and amisulpride (n = 2). Approximately half of the available data on the M/P ratio, RID, and infant drug plasma levels included olanzapine. Relatively adequate reports suggest that olanzapine has low RID values. Limited reports suggest low RID values for quetiapine and ziprasidone, moderate RID values for risperidone/paliperidone and aripiprazole, and high RID values for amisulpride. Antipsychotic levels were undetectable in the plasma of most of the exposed infants. Other than clozapine, adverse events were rarely reported in infants exposed to SGAs. CONCLUSIONS: The current data suggest that SGAs seem to be relatively safe in the exposed breastfed infants for short-term usage. However, additional studies, in particular for antipsychotics other than olanzapine, examining short-term and especially long-term effects of SGAs on the breastfed infants are required.

Mood stabilizers during breastfeeding: a systematic review of the recent literature.

OBJECTIVE: This review examined the safety of mood stabilizers in exposed breastfed infants. METHODS: PubMed was searched for English language reports between 1 January 1995 and 30 August 2015 by using combinations of key words breastfeeding, lactation, postpartum period, puerperium, mood stabilizers, lithium, lamotrigine, valproate, carbamazepine, and oxcarbazepine. Case reports, case series, and prospective or cross-sectional studies including relevant data such as relative infant dose, milk-to-plasma ratio, infant drug plasma levels, and adverse events were identified. RESULTS: A total of 26 of 604 relevant reports in PubMed were included in the study. These reports included lamotrigine (122 cases in 12 reports), lithium (26 cases in five reports), carbamazepine (64 cases in five reports), valproate (nine cases in three reports), and oxcarbazepine (two cases in two reports). Of 26 reports, one report included both carbamazepine and valproate. The reports suggest that a considerable amount of lithium and lamotrigine are excreted into breast milk. There is a paucity of data on valproate and oxcarbazepine; however, the infant/maternal ratio of serum drug concentration seems to be lower in valproate exposure compared to other mood stabilizers. The incidence of adverse events in infants exposed to mood stabilizers is reported to be very low. CONCLUSIONS: The current data suggest that mood stabilizers can be prescribed without any adverse events in most infants in lactating women. The available reports also suggest a low prevalence rate of laboratory abnormalities including hepatic, kidney, and thyroid functions in the infants. Additional studies examining short-term and especially long-term effects of mood stabilizers on breastfed infants are required.

Breastfed Infants Exposed to Combined Antipsychotics: Two Case Reports.

Manic episodes of bipolar disorder and psychotic exacerbations of schizophrenia, for which the antipsychotic drugs are most commonly prescribed, are frequently seen in the postpartum period. Despite the existence of single use of antipsychotics, data on safety of combined antipsychotics on the breastfed infants are limited. This report presents the clinical outcome of 2 infants exposed to combined antipsychotic during the lactation period.

Hypomanic episode improved spontaneously after isolated acute cerebellar infarct: a case report.

Cerebellum provides functions to be maintained at a basal level by regulating mental performance by means of functional and anatomic links critical for cognition structures. The status emerging with the determination of cognitive and affective disorders after the posterior lobe injury of the cerebellum was termed as a "Cerebellar Cognitive Affective Syndrome" by Schmahmann and Sherman in 1998. The present report presents the clinical course in a patient with a diagnosis of hypomanic episode after cerebellar infarct.

Sertraline-induced periorbital purpura: a case report.

OBJECTIVE: The incidence of mild to severe levels of spontaneous bleeding due to the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low. Although the exact mechanism is not known, it is thought that inhibition of the serotonin transporter together with a decrease in platelet serotonin could be responsible for the bleeding. Therefore, the use of SSRIs in conjunction with anti-aggregants may predispose to or exacerbate the risk of bleeding. In this case report, we describe a 44-year-old female patient with a diagnosis of anxiety disorder who spontaneously developed periorbital purpura during treatment with sertraline. CONCLUSION: Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline.

Low-dose imipramine for treatment of panic disorder during pregnancy: a retrospective chart review.

Although imipramine is one of the antidepressants that could be effective in the treatment of panic disorder, data on its usage for this diagnosis in the pregnancy period are limited. This report presents the results of 16 pregnant women with panic disorder without comorbid diagnosis who underwent low-dose imipramine (10-40 mg/d) treatment. According to the Clinical Global Impression-Improvement Scale, 12 (75%) of 16 women responded to the treatment. The results suggest that low-dose imipramine may be useful for the treatment of panic disorder during pregnancy.

Birth weight and preterm birth in babies of pregnant women with major depression in relation to treatment with antidepressants.

OBJECTIVE: It is unclear whether antidepressant treatment has a preventive effect on negative neonatal outcomes due to major depression in pregnant women. The objective of the present study was to compare women with major depression treated with antidepressants, untreated women with major depression, and healthy women during pregnancy with respect to birth weight and preterm birth. METHODS: The study sample included a total of 23 women taking antidepressant medication, 36 women who were not taking antidepressant medication for major depression during pregnancy, and 30 healthy women. Major depression was diagnosed via the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. RESULTS: The study groups were similar with respect to sociodemographic characteristics. Compared with infants of healthy control subjects, infants of untreated major depressed women had significantly lower birth weight and shorter gestational age at delivery. There is no significant difference between infants of major depressed women treated with antidepressants and infants of healthy subjects for these variables. CONCLUSIONS: Our results suggest that antidepressants may have beneficial effects on the risk of low birth weight and preterm birth in the infants of depressed women.

Psychiatric disorders and association with quality of sleep and quality of life in patients with chronic pain: a SCID-based study.

OBJECTIVE: We aimed to determine Axis-I psychiatric disorders in patients with chronic pain (CP) and compare control subjects determined by a structured clinical interview. Another objective of the study was to examine whether there is an association between psychiatric disorders and quality of sleep, quality of life, and demographic and clinical characteristics in patients with CP. DESIGN: The study sample was comprised of 108 patients with CP and 54 control subjects without pain. Psychiatric interviews were conducted with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV (SCID). Also used were the Hospital Anxiety and Depression Scale, Hamilton Depression Inventory, Short Form-36, and Pittsburgh Sleep Quality Index (PSQI). RESULTS: The rate of any Axis-I psychiatric disorder stood at 66.7% (any mood disorder, 50%; any anxiety disorder, 33.3%; any somatoform disorder, 20.4%; any substance use disorder, 16.6%), significantly more common in the patients' group compared with the control group. The most common psychiatric disorder was major depression (49.1%) in subjects with CP. Female gender, numbers of localization, and neck and back localizations were significantly higher in the SCID (+) group than the SCID (-) group. A statistically significant difference was observed between the SCID (+) and SCID (-) groups regarding visual analogue scale, depression and anxiety scores, mental component summary score, and global PSQI scores. CONCLUSION: Results of this study suggest that psychiatric morbidity in patients with CP is frequently seen and may adversely affect quality of sleep and quality of life of the patients. Therefore, the patients with CP should be examined with respect to their mental status.

Neuroinflammation in the fetus exposed to maternal obsessive-compulsive disorder during pregnancy: a comparative study on cord blood tumor necrosis factor-alpha levels.

OBJECTIVE: The relationship between maternal psychiatric disorders and fetal neurodevelopment is unclear. Obsessive-compulsive disorder (OCD) is relatively frequent during pregnancy. The study aimed to investigate whether maternal OCD during pregnancy affects fetal circulating tumor necrosis factor-alpha (TNF-α) levels, an important pro-inflammatory cytokine, by comparing cord blood TNF-α levels in newborn infants of women with and without OCD. METHODS: The study sample included 7 women with OCD and 30 healthy women. OCD and other psychiatric diagnoses were screened by means of the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The blood sample for the determination of TNF-α level was obtained from the umbilical cord during delivery. RESULTS: Cord blood TNF-α levels in newborn infants exposed to maternal OCD were significantly higher compared to non-exposed infants. Maternal anxiety symptom level was found to positively correlate with cord blood TNF-α levels in newborn infants of women with OCD. CONCLUSION: The study results imply that maternal OCD during pregnancy may lead to neuroinflammation in the developing fetal brain through higher levels of circulating TNF-α.