Administration of antidepressant drugs – principally selective serotonin reuptake inhibitors (SSRIs) – may induce clinically significant ‘apathy’ which can affect treatment outcomes adversely. We aimed to review all relevant previous reports.

We performed a PUBMED search of English-language studies, combining terms concerning psychopathology (e.g. apathy) and classes of antidepressants (e.g. SSRI).

According to certain inclusion (e.g. use of DSM/ICD diagnostic criteria) and exclusion (e.g. presence of a clinical condition that may induce apathy) criteria, 50 articles were eligible for review. Together, they suggest that administration of antidepressants – usually SSRIs – can induce an apathy syndrome or emotional blunting, i.e. a decrease in emotional responsiveness, to circumstances which would have triggered intense mood reactions prior to pharmacotherapy. The reported prevalence of antidepressant-induced apathy ranges between 5.8 and 50%, and for SSRIs ranges between 20 and 92%. Antidepressant-induced apathy emerges independently of diagnosis, age, and treatment outcome and appears dose-dependent and reversible. The main treatment strategy is dose reduction, though some data suggest the usefulness of treatment with olanzapine, bupropion, agomelatine or amisulpride, or the methylphenidate–modafinil–olanzapine combination.

Antidepressant-induced apathy needs careful clinical attention. Further systematic research is needed to investigate the prevalence, course, aetiology, and treatment of this important clinical condition.

Galactorrhea wiht antidepressants SSRIs or SNRI is a rarely adverse effect. Some authors believe that the risk of galactorrhea in women who use SSRIs is 8 times higher than in patients treated with other types of drugs. Serotonin is believed to be a potent physiological stimulator of prolactin release.Prolactin stimulates the growth of the mammary glands and the galactorrhea. The SSRIs would activate the serotonergic pathways, these in turn would stimulate the release of prolactin directly in the pituitary and in the hypothalamus, inhibiting the release of dopamine and increasing the release of stimulating factors. The main inhibitor of prolactin secretion is dopamine.

The objective is to reveal this rare complication through the report of a clinical case

A 45-year-old woman with a diagnosis of mixed anxiety-depressive disorder. Treatment with 20 mg of escitalopram was started, with a good therapeutic response, but with breast pain and swelling. She was switched to duloxetine 60 mg, with a good response and adequate tolerance. At 6 months of treatment, she begins to present breast pain and yellow-green breast discharge, with elevated prolactin levels and normal cranial MRI.

She was diagnosed with functional hyperprolactinemia, and treatment with vortioxetine was started. Finally, the Prolactin levels normalize.

Galactorrhea is a very rare and annoying side effect that can lead to discontinuation of treatment and requires a change in the therapeutic strategy.

No significant relationships.

The study aimed to investigate severe hair loss related to psychotropic drugs (PDs) by using data from the drug safety programme Arzneimittelsicherheit in der Psychiatrie (AMSP).

Data on PD utilization and reports of severe PD-related hair loss were collected in 83 psychiatric hospitals in Austria, Germany and Switzerland during the period 1993–2013.

Out of 432, 215 patients under surveillance, 404, 009 patients were treated with PDs for the main indications of depression, schizophrenic disorder, neurosis, mania, and organic psychosis. Severe hair loss related to PD treatment was reported in 43 cases (0.01%). The rates of hair loss under antipsychotic drugs were slightly lower than the mean rates of all PDs and antidepressant drugs. Valproic acid was related to the highest risk. In 6 of the 43 cases, hair loss was imputed to multiple drugs, with 4 cases imputed to double drug combinations and 2 cases to triple combinations. Rates of severe hair loss under valproic acid (VPA) and lithium salts were distinctly lower as compared with the overall rates reported in literature. Severe hair loss under PD treatment was reported significantly more often in female patients than in male patients (p < 0.01).

The rate of severe PD-related hair loss was very low in the present survey. The large number of patients included in this multicentre study allows for assessment and comparison of hair loss rates related to different PDs and groups of PDs and provides new and supplementary information on PD-related hair loss.

Although monoaminergic-targeted drugs have prompted great advances in the development of treatments for depression, the need for new options persists, since these drugs still have a delayed clinical effect and most patients do not respond properly to them. Recently, the observation of the antidepressant effects of ketamine brought on a new wave of studies regarding the comprehension of the neurobiology of depression and the development of new and more effective antidepressant drugs.

Thus, in this paper, we present a historical review of the development of monoaminergic antidepressant drugs and the role of ketamine as the introductory agent of a new era in the research of the neurobiology of depression.

Firstly, we review how the pharmacological treatment for major depression started, and we point out the main drugs discovered, the researchers involved, and how the studies developed have contributed to the understanding of the neurobiology of depression. Secondly, the major problems regarding the clinical efficacy and acceptance of these drugs are discussed, and the introduction of the glutamatergic system as a target for antidepressant drugs is presented. Finally, we review how ketamine revealed itself as an exciting option towards obtaining pharmacological agents to treat depression, through the understanding of biological markers.

Ketamine contributed to confirm that different targets of the glutamatergic system and neurotrophic pathways are strictly related to the neurobiology of depression. There are several antidepressant drugs based on ketamine’s mechanism of action already in the pipeline, and glutamatergic-targeted antidepressants may be on the market in the near future.

Studies have demonstrated a decreased platelet ADAM10 expression in patients with Alzheimer's Disease (AD), classifying this protein as a blood-based AD biomarker. About 50% of the patients with AD are diagnosed with depression, which is commonly treated with tricyclic and tetracyclic antidepressants, monoaminoxidade (MAO) inhibitors and, more preferably, with selective serotonin reuptake inhibitors (SSRIs). Considering that a large proportion of patients with AD takes antidepressant medications during the course of the disease we investigated the influence of this medication on the expression of platelet ADAM10, which is considered the main α-secretase preventing beta-amyloid (βA) formation.

Blood was collected for protein extraction from platelets. ADAM10 was analyzed by using western blotting and reactive bands were measured using β-actin as endogenous control.

Platelet ADAM10 protein expression in patients with AD was positively influenced by serotoninergic medication.

More studies on the positive effects of serotonergic antidepressants on ADAM10 platelet expression should be performed in order to understand its biological mechanisms and to verify whether these effects are reflected in the central nervous system. This work represents an important advance for the study of AD biomarkers, as well as for more effective pharmacological treatment of patients with AD and associated depression.

Concerns have been expressed about possible adverse effects of the use of antidepressant medication during pregnancy, including risk for neonatal pathology and the presence of congenital malformations.

Data from the Swedish Medical Birth Register (MBR) from 1 July 1995 up to 2007 were used to identify women who reported the use of antidepressants in early pregnancy or were prescribed antidepressants during pregnancy by antenatal care: a total of 14 821 women with 15 017 infants. Maternal characteristics, maternal delivery diagnoses, infant neonatal diagnoses and the presence of congenital malformations were compared with all other women who gave birth, using the Mantel–Haenszel technique and with adjustments for certain characteristics.

There was an association between antidepressant treatment and pre-existing diabetes and chronic hypertension but also with many pregnancy complications. Rates of induced delivery and caesarean section were increased. The preterm birth rate was increased but not that of intrauterine growth retardation. Neonatal complications were common, notably after tricyclic antidepressant (TCA) use. An increased risk of persistent pulmonary hypertension of the newborn (PPHN) was verified. The congenital malformation rate was increased after TCAs. An association between use of paroxetine and congenital heart defects was verified and a similar effect on hypospadias was seen.

Women using antidepressants during pregnancy and their newborns have increased pathology. It is not clear how much of this is due to drug use or underlying pathology. Use of TCAs was found to carry a higher risk than other antidepressants and paroxetine seems to be associated with a specific teratogenic property.

This study examined therapist–patient interactions during clinical management with antidepressant medication and pill-placebo.

The sample consisted of 80 patients on active medication and 40 patients in a pill-placebo condition from a randomized controlled trial for moderate to severe depression. Pharmacotherapist–patient interactions were characterized using observer ratings of the therapeutic alliance, pharmacotherapist-offered facilitative conditions, pharmacotherapist adherence to clinical management treatment guidelines and pharmacotherapist competence. Patients, therapists and raters were blind to treatment condition and outcome.

Provision of greater non-specific support (facilitative conditions) in early sessions predicted less subsequent improvement in depressive symptoms for patients receiving pill-placebo but not those receiving active medications, for which none of the process ratings predicted subsequent change. Early symptom change predicted later alliance and adherence in both conditions and therapist competence in the active condition.

Higher levels of support in early sessions predict poorer subsequent response among placebo patients. It remains unclear whether patients who are likely to be refractory elicit greater non-specific support or whether the provision of such support has a deleterious effect in unmedicated patients. Differences in treatment process variables between conditions late in treatment are likely to be largely a consequence of symptom relief produced by active medications.

Guidelines for the treatment of depression regularly emphasize that pharmacotherapy of depression should be accompanied by supportive counseling and other psychotherapeutic interventions. It is unknown which role psychiatrists in routine care give to such verbal therapies.

in a drug utilization study of venlafaxine, psychiatrists in private practice and in hospitals were asked to tell what non-pharmacological therapies they saw as an important part of the treatment of the present depressive episode. Additionally patient characteristics, treatment variables, setting characteristics and physician characteristics were assessed.

Psychiatrists reported some kind of verbal therapies in 19.0% of outpatients and 36.8% of inpatients. Verbal therapies were reported more often for younger patients, who got more double diagnoses and were more severely ill. Patients with verbal therapies got more psychotropic medication. in the inpatient setting verbal therapies were related to generally more treatment overall and a higher rate of treatment response. in both treatment settings verbal therapies were related to lower rates of discontinuation of the antidepressant.

Verbal interactions are part of any patient–physician encounter and should be theory guided as part of the therapeutic process in the treatment of depressive disorders. Under this assumption the rate of patients for which psychiatrists reported some kind of verbal therapy as explicit part of their treatment could be higher. More research is needed on patient guidance, counseling and supportive psychotherapy in psychiatry.