Paroxetine is a highly potent and selective inhibitor of serotonin reuptake, with in vitro potency greater than that of fluoxetine, fluvoxamine, and sertraline. It has little affinity for a wide variety of neurotransmitter receptors, including catecholaminergic or histaminergic systems, in marked contrast to the tricyclic antidepressants. Paroxetine undergoes first-pass metabolism that is partially saturable to give metabolites that are pharmacologically inactive in vivo, unlike those of fluoxetine or sertraline.

Depression is commonly associated with suicidal thoughts and behaviour. The effect of the antidepressant, paroxetine, on suicidality in depressed patients has been assessed by retrospective analysis of the worldwide database of short-term clinical trials. Data were analysed on 2963 patients treated with paroxetine. 554 placebo patients, and 1151 patients treated with an active control. The results clearly demonstrate the beneficial effect of antidepressant therapy on suicidal ideation. Paroxetine was not associated with the emergence of suicidality, which appears to be a feature of depressive disorder unrelated to antidepressant therapy.

Panic disorder is a chronic condition for many patients and can be socially, emotionally and occupationally disabling. Until recently, clomipramine and alprazolam were the only drugs approved for its treatment. While widely used in the US and Europe, both belong to drug classes (tricyclics and benzodiazepines) with well-recognised side effects that can be problematic and thus limit their use. Recently, paroxetine became the first selective serotonin reuptake inhibitor to receive approval and licensing for panic disorder.

The short- and long-term efficacy and tolerability of paroxetine in panic disorder has been established in clinical trials of almost 1,000 patients meeting Diagnostic and Statistical Manual (DSM)-IIIR criteria for panic disorder, with or without agoraphobia. In a 12-week double-blind study of 120 panic patients receiving standardised cognitive therapy, paroxetine was significantly more effective than placebo in reducing panic attack frequency. In a 12-week placebo-controlled comparison in 367 panic patients, paroxetine was at least as effective as clomipramine and better tolerated. There was also some evidence that paroxetine had an earlier onset of action than clomipramine.

A 9-month extension of the placebo-controlled comparison with clomipramine showed that the efficacy of paroxetine and clomipramine is maintained when treatment is continued into the longer term. In a relapse prevention study, 105 responders to 3 months' treatment with paroxetine or placebo were re-randomised, either to continue existing treatment or to receive placebo for 3 months. Only 5% of patients who continued to take paroxetine experienced a relapse compared with 30% of those who switched to placebo (P = 0.002). Paroxetine was generally well tolerated. In the short-term trials, the frequency of withdrawals due to adverse events (7.3%) was lower than that for placebo (11.4%) or clomipramine (14.9%). In the longer term, the dropout rate due to adverse events increased in the clomipramine group (19.0%) but was unchanged in the paroxetine group (7.4%). Since most patients with panic disorder will require prolonged treatment, the long-term tolerability of paroxetine and its lack of potential for dependence are important advantages that will encourage good compliance with treatment and improve the quality of life of patients.

Long-term treatment with antidepressants is now an accepted strategy in the management of depression. The demonstration of efficacy in this setting requires specific placebo-controlled trials of patients with recurrent depression studied after an adequate period of euthymia and for a long period of follow-up. This review examines the evidence for the prophylactic efficacy of antidepressant therapy with particular emphasis on the selective serotonin reuptake inhibitor, paroxetine.

The effect of paroxetine on symptoms of anxiety associated with depression were assessed by meta-analysis of data on the use of paroxetine (n = 2963), active control (n = 1151), and placebo (n = 554) in six-week clinical trials. Paroxetine significantly reduced psychic anxiety by comparison with placebo from week 1 and was more effective than active control from week 2. Paroxetine improved somatic anxiety from week 4 of treatment. There was no association between antidepressant therapy and the emergence of anxiety symptoms in patients with little or no baseline anxiety. Paroxetine resolved baseline symptoms of agitation from week 1 of treatment, and both paroxetine and active control prevented the emergence of agitation. There was no difference between placebo and antidepressant therapy in the frequency of adverse events indicative of increased arousal. The results indicate the utility of paroxetine in depressed patients presenting with associated anxiety symptoms.

The tolerability and safety of treatment with paroxetine have been assessed by analysis of a clinical trial database that extends to 4126 patients treated with paroxetine, 1954 patients on active control, and 625 placebo patients. A total of 451 patients were exposed to paroxetine for periods of 1 or more years. Paroxetine was generally better tolerated than active control and was associated with a lower frequency of manic reactions in bipolar patients and fewer seizures than active control. Paroxetine appears to offer a differential advantage in reducing suicidal thoughts; the number of suicides and attempted suicides per patient exposure year were lower for paroxetine than for other antidepressants or placebo.

Meta-analyses of 417 patients diagnosed either prospectively (316 US patients) or retrospectively (101 European patients) as suffering from melancholia according to DSM III criteria have shown that paroxetine was significantly better than placebo with respect to all outcome measures. There was no significant difference between active control and placebo in these analyses. In a group of 216 severely depressed hospitalised patients with a HAMD score of 25 or more, paroxetine was as effective as active control.

In a double blind controlled study, rTMS results in a similar antidepressant effect to sham in combination with paroxetine. Both groups had the same delay in scale’s scores improvement. rTMS seems not to be efficient as an add-on treatment to pharmacological medication in non-resistant major depression.

A female neonate with in utero selective serotonin reuptake inhibitor exposure presented with bradycardia shortly after birth. Electrocardiography showed severe QT prolongation and second-degree atrioventricular block. Over time QT-times spontaneously normalised and genetic testing did not show mutations associated with long QT syndrome making maternal selective serotonin reuptake inhibitor usage the most likely explanation for the observed severe transient neonatal QT prolongation.

Introduction: To investigate the effects of paroxetine (PAR) on motor and cognitive function recovery in patients with non-depressed ischemic stroke (nD-AIS).

Methods: One hundred sixty-seven patients hospitalized for non-depressed acute ischemic stroke were selected and divided into treatment (T) and control (C) groups using a random number table. All patients received conventional secondary ischemic stroke prevention and rehabilitation training; patients in Group T additionally received treatment with PAR (10 mg/day during week 1 and 20 mg/day thereafter) for 3 months. The follow-up observation lasted 6 months. The Fugl–Meyer motor scale (FMMS), Montreal cognitive assessment (MoCA), and Hamilton depression scale (HAMD) were used on D0, D15, D90, and D180 (T0, 1, 2, and 3, respectively; D180 = 90 days after treatment cessation) after study initiation, and scores were compared between the groups.

Results: The FMMS and MoCA scores differed significantly between Groups T and C at T2 and T3 (p < .05); by contrast, these scores did not differ significantly between the groups at T1 (p > .05). Furthermore, the HAMD scores differed significantly between the two groups at T3 (p < .05), but not at T1 and T2 (p > .05).

Conclusions: PAR treatment may improve motor and cognitive function recovery in patients with nD-AIS. Moreover, PAR may reduce the occurrence of depression after stroke.

In well-differentiated primary cultures of mouse astrocytes, which express no serotonin transporter (SERT), the ‘serotonin-specific reuptake inhibitor’ (SSRI) fluoxetine leads acutely to 5-HT2B receptor-mediated, transactivation-dependent phosphorylation of extracellular regulated kinases 1/2 (ERK1/2) with an EC50 of ~5 μM, and chronically to ERK1/2 phosphorylation-dependent upregulation of mRNA and protein expression of calcium-dependent phospholipase A2 (cPLA2) with ten-fold higher affinity. This affinity is high enough that fluoxetine given therapeutically may activate astrocytic 5-HT2B receptors (Li et al., 2008, 2009). We now confirm the expression of 5-HT2B receptors in astrocytes freshly dissociated from mouse brain and isolated by fluorescence-activated cell sorting (FACS) and investigate in cultured cells if the effects of fluoxetine are shared by all five conventional SSRIs with sufficiently high affinity to be relevant for mechanism(s) of action of SSRIs. Phosphorylated and total ERK1/2 and mRNA and protein expression of cPLA2a were determined by Western blot and reverse transcription polymerase chain reaction (RT-PCR). Paroxetine, which differs widely from fluoxetine in affinity for SERT and for another 5-HT2 receptor, the 5-HT2C receptor, acted acutely and chronically like fluoxetine. One micromolar of paroxetine, fluvoxamine or sertraline increased cPLA2a expression during chronic treatment; citalopram had a similar effect at 0.1–0.5 μM; these are therapeutically relevant concentrations.

Individuals with cancer have two to four times an increased risk of depressive disorders compared to the general population. Depressive symptoms are related to impaired daily life functioning and a rise in health care utilization. Pharmacological treatments for depression are usually effective to reduce depressive symptoms, but sometimes lead to serious adverse reactions. We describe a cancer patient who developed sudden psychological and behavioral abnormalities after administration of the antidepressant paroxetine. Impulsive and aggressive symptoms are a so-called activation syndrome that can cause violent or suicidal tendencies. Palliative care staff should pay close attention to these potentially lethal reactions and make an immediate and correct diagnosis.