Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressants. Other clinical indications for SSRI use include anxiety disorders, obsessive-compulsive disorder, panic disorders, and eating disorders. Compared to their predecessors, the monoamine oxidase inhibitors and tricyclic antidepressants, SSRIs are associated with fewer toxic effects.[1]  Individual SSRIs differ from each other regarding structure and pharmacokinetics but, as a group, they act by potentiating the action of serotonin. SSRIs are less cardiotoxic than many first-generation antidepressants, but there is still evidence that they inhibit sodium, calcium, and potassium ion channels at concentrations near therapeutic levels.[2] Citalopram and escitalopram are known to cause QTc prolongation.[3][4] There also have been reports of atrial fibrillation and bradycardia related to fluoxetine use.[5] Adverse effects of SSRIs are vague and nonspecific but include hyponatremia, anorgasmia, sedation, stimulation, and gastric irritation.[6][7] Seizures are uncommon but have been reported; Isbister et al.[8] reported a seizure incidence of 1.9%. They may also inhibit platelet secretion, aggregation, and plug formation.[9] Patients with adverse effects from SSRIs will present with a range of symptoms, and some researchers have advocated for the term “serotonin toxicity” rather than “serotonin syndrome” to highlight that this condition is a spectrum of symptoms rather than a single clinical entity. [10][11] In patients with mild symptoms, the benefit they receive from the prescribed SSRI may outweigh the negative side effects.

Headache is a neurologic disorder that displays gender dichotomy. It is well established that there is a strong link between migraine headache and sex hormones, specifically estrogen, which influences the severity of migraines during the menstrual cycle, pregnancy, and menopause. Furthermore, the epidemiology of headaches during pregnancy and the postpartum period is very distinct from that in males or nonpregnant females, in part due to the hemodynamic and hematologic changes that occur during pregnancy. These changes put women at higher risk for cerebral venous thrombosis, hemorrhagic stroke, and hypertensive disorders of pregnancy like preeclampsia, eclampsia, posterior reversible encephalopathy syndrome, and reversible cerebral vasoconstriction syndrome. Headache in pregnancy and the puerperium can be a cause of heightened anxiety in most women, who are concerned not only about the effect of the headache itself on the pregnancy but also about the effect of the treatment options on the pregnancy and the fetus. In this review, we discuss the latest literature on type and distribution of headaches during pregnancy and the postpartum period, and provide a digestible overview of the safety profile of commonly used abortive and prophylactic medications. We also discuss important considerations when treating migraine during menopause.

Early life immune challenges are risk factors for neurodevelopmental disorders. In adolescence, they elicit behavioral symptoms that resemble clinical disorders. Stressors during this time may alter signaling from the gut microbiome, which increases the risk for psychiatric disorders. It was hypothesized that adolescent immune challenges may interact with a gut bacterial product, the short-chain fatty acid, propionic acid (PPA), to potentiate symptoms of anxiety and sensory abnormality. The present study investigated the effects of repeated lipopolysaccharide (LPS) exposure during early adolescence, on the behavioral effects of PPA in late adolescence and adulthood. Male adolescent rats were injected with LPS (0.2 mg/kg i.p.) or the vehicle on postnatal days (P) 28, P30, P32, and P34. They were later administered either PPA (500 mg/kg i.p.) or the vehicle during late adolescence on P40 and P43, and were subsequently tested on the light-dark anxiety test and acoustic startle response, respectively. In adulthood, the rats were again injected with PPA or the vehicle and tested on the light-dark and acoustic startle tasks on P74 and P77. The results of this study showed that LPS and PPA both decreased locomotor activity. PPA reduced vertical activity, percent prepulse inhibition, and acoustic startle response magnitude. LPS increased anxiogenic behaviors and induced a delayed increase in acoustic startle response magnitude in adulthood. Although no LPS and PPA interactions were found, the results of this study suggest that early adolescent immune activation can induce long-term behavioral changes that resemble the complex phenotypes of clinical disorders.

Opioid misuse and dependence are major medical and social concerns worldwide. Buprenorphine/naloxone combination (BNC) is a drug that has misuse potential and is used to treat opioid dependence, including buprenorphine and naloxone. Buprenorphine shows its pharmacological effects by binding to opioid receptors. Buprenorphine is a partial agonist and has smaller maximal effects compared to those of full agonists (heroin, methadone). Naloxone is a non-selective opiate antagonist added to buprenorphine for the prevention of intravenous diversion. BNC is used in the treatment of opioid dependence for detoxification and maintenance. The drug should be used as a sublingual film tablet. Pregabalin is used in the treatment of neuropathic pain, epilepsy and anxiety disorders. It is increasingly being reported as possessing a potential for misuse. In this article, we present a case of intravenous BNC and concomitant oral pregabalin misuse that developed in a monitored and treated patient for the reason of opioid dependence.

Anxiety disorders arise from disruptions among the highly interconnected circuits that normally serve to process the streams of potentially threatening stimuli. The resulting imbalance among these circuits can cause a fundamental misinterpretation of neural sensory information as threatening and can lead to the inappropriate emotional and behavioral responses observed in anxiety disorders. There is considerable preclinical evidence that the GABAergic system, in general, and its α2- and/or α5-subunit-containing GABA(A) receptor subtypes, in particular, are involved in the pathophysiology of anxiety disorders. However, the clinical efficacy of GABA-A α2-selective agonists for the treatment of anxiety disorders has not been unequivocally demonstrated. In this review, we present several human pharmacological studies that have been performed with the aim of identifying the pharmacologically active doses/exposure levels of several GABA-A subtype-selective novel compounds with potential anxiolytic effects. The pharmacological selectivity of novel α2-subtype-selective GABA(A) receptor partial agonists has been demonstrated by their distinct effect profiles on the neurophysiological and neuropsychological measurements that reflect the functions of multiple CNS domains compared with those of benzodiazepines, which are nonselective, full GABA(A) agonists. Normalizing the undesired pharmacodynamic side effects against the desired on-target effects on the saccadic peak velocity is a useful approach for presenting the pharmacological features of GABA(A)-ergic modulators. Moreover, combining the anxiogenic symptom provocation paradigm with validated neurophysiological and neuropsychological biomarkers may provide further construct validity for the clinical effects of novel anxiolytic agents. In addition, the observed drug effects on serum prolactin levels support the use of serum prolactin levels as a complementary neuroendocrine biomarker to further validate the pharmacodynamic measurements used during the clinical pharmacological study of novel anxiolytic agents.