An overview of the most important side effects of the psychotropic medication.
I. ANTIDEPRESSIVE DRUGS TRICYCLIC ANTIDEPRESSANTS
* Cardiovascular side effects
Various aspects of the cardiotoxicity of tricyclic antidepressants have been reviewed, including direct myocardial actions and hypotension. Tricyclic antidepressants are highly concentrated in the myocardium; this may account for the vulnerability of the heart as a target organ, as well as for inconsistently and inconclusively reported relations between plasma drug concentrations and specific manifestations of cardiac toxicity.
These drugs can interfere with the normal rate, rhythm, and contractility of the heart through actions both on the nerve and the muscle, that are mediated by at least four different mechanisms (singly, in combination, or due to imbalance), including an anticholinergic action, interference with reuptake of catecholamines, direct myocardial depression, and alterations in membrane permeability due to lipophilic and surfactant properties.
Changes in conduction and repolarization cause prolongation of the PR, QRS, and QT intervals and flattening or inversion of T-waves on routine electrocardiograms; conduction delay occurs distal to the atrioventricular node and appears as a prolonged HV interval (the time from activation of the bundle of His to contraction of the ventricular muscle).
As many as 20% of patients taking adequate doses of a tricyclic antidepressant, experience marked postural hypotension. This effect is not consistently correlated with plasma concentrations and tolerance does not develop during treatment   . The mechanism for this effect is uncertain; it has been attributed to a peripheral antiadrenergic action, to a myocardial depressant effect, and to an action mediated by alpha-adrenoceptors in the central nervous system   .
* Respiratory side effects
There has been one case report of reduced ventilatory response to hypercapnia after nortriptyline in a woman with chronic obstructive pulmonary disease .
* Nervous system side effects Miscellaneous symptoms that have been attributed to the tricyclic antidepressants include fatigue, weakness, dizziness, headache, and tremor; patients are likely to fall because of these disturbances .
Several organs are the target for the anticholinergic (antimuscarinic) activity of the tricyclic antidepressants. They constitute the most common and troublesome adverse effects of the tricyclic antidepressants, but the peripheral anticholinergic actions can also be put to therapeutic use in conditions such as irritable bowel syndrome, premature ejaculation, and nocturnal enuresis.
Regarding the extrapyramidal side effects, tricyclic antidepressants are often listed among the many drugs that can produce buccofaciolingual or choreoathetoid movements .
* Metabolism and endocrine side effects
The tricyclic antidepressants (TCAs) can lead to increased weight, and this is primarily due to increased appetite and carbohydrate craving, that are likely the result of blocking histamine and 5-HT2 receptors in the brain. TCAs can also raise serum cholesterol and triglycerides; however, it is not clear if those effects are secondary to the weight gain .
* Gastrointestinal side effects
This treatment can cause simple a bowel disturbances or more serious complications like paralytic ileus, which can be life-threatening, especially in the elderly .
The incidence of gastroesophageal reflux disease has been reported to be higher in depressed patients (14.2 per 1000 person per year; 95% CI1/4 13.6, 14.8) compared with controls (8.3 per 1000 person per year; 95% CI1/4 1.60, 1.85) in a large cohort study; the hazard ratio was 1.72 (95% CI1/4 1.34, 2.20)  and the researchers speculated that the anticholinergic effects of tricyclic antidepressants may reduce lower esophageal sphincter pressure, leading to more frequent episodes of reflux .
* Hematologic side effects
Occasional cases of blood dyscrasias, agranulocytosis or non-thrombocytopenic purpura have been associated with this treatment    .
* Psychiatric side effects
Musical hallucinations have been reported in association with clomipramine  and it is widely believed that there is a significant risk that tricyclic antidepressants can precipitate mania or rapid cycling in up to 10% of patients, and that various factors increase this possibility, including being female or younger, having an earlier onset of illness, and having a positive first degree family history. 
SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)
* Nervous system side effects
In a case-crossover study there was an association between antidepressant drug use and an increased risk of stroke (AOR % 1.48) . An excess risk of stroke with antidepressant use was more apparent for ischemic strokes (AOR% 2.52) than with hemorrhagic strokes (AOR% 1.92). SSRIs were associated with the highest risks for all strokes and ischemic strokes (AOR% 4.22 and 4.11 respectively), and other antidepressants (SNRIs, Trazodone and Venlafaxine) for hemorrhagic stroke (AOR % 5.40, SSRIs 4.24). 
* Cardiovascular side effects
The SSRIs appear to have a better cardiovascular safety. Only Citalopram may be associated with QTc prolongation. The effect of Citalopram on the QTc interval has been confirmed in a cross-sectional study using ECG and clinical data from electronic health records . In that study, the relationship between dosage of a number of antidepressants and QTc was examined in 38 397 patients who had an ECG following prescription of an antidepressant. 
* Metabolic and Endocrine side effects Uguz et al. examined weight gain in patients taking SSRI in a cross-sectional study of 362 consecutive psychiatric patients taking antidepressants for 6 to 36 months. Over half of the patients studied (55.2%) gained weight with 40.6% gaining 7% or more of their initial weight. Citalopram, Escitalopram, Sertraline, Paroxetine, Venlafaxine, Duloxetine and Mirtazapine, but not Fluoxetine, were all associated with significant weight gain. Blumenthal et al. identified 22 610 adult patients who had commenced an antidepressant and for whom weight data were available in a regional health care system, assessing the association between individual antidepressants and weight change, over 12 months after treatment initiation. They found the greatest weight gain in patients taking Mirtazapine and Paroxetine, which was similar in magnitude to that observed with Citalopram. Compared with Citalopram, a significantly decreased rate of weight gain was observed in patients treated with Bupropion, Amitriptyline and Nortriptyline. Noting limited empirical data on antidepressant use and weight change in younger patients, Cockerill et al. performed a historical cohort study assessing change in BMI (body mass index) associated with antidepressant use in overweight adolescents with a depressive disorder. They found that BMI was significantly increased only in those adolescents treated with SSRIs. 
Treatment with SSRIs and SNRIs was associated with an increased risk of hyperprolactinemia (reporting odds ratio, ROR 1/4 3.3) in a study using data from the French Pharmacovigilance Database; the risk was particularly increased with fluvoxamine (ROR1/4 4.5), Citalopram (ROR 1/4 3.9), and Fluoxetine (ROR1/4 3.6); Sertraline, Duloxetine, and Milnacipran were not associated with an increased risk. 
* Hematologic side effects
Bleeding abnormalities associated with antidepressants are becoming more commonly reported, leading to questions about the safety and appropriateness of these medications in a number of relevant clinical scenarios and patient populations. Over the last decade or so there have been a number of reports of increased risk of bleeding as sociated with selective serotonin reuptake inhibitors (SSRI), like gastrointestinal bleeding, postpartum hemorrhage, brain hemorrhage or perioperative hemorrhage     . Although there have been numerous reports concerning antidepressants and bleeding, relatively few have examined direct in vitro platelet effects, with most examining effects on platelet aggregation. A small study examined the effect of two SSRIs (Sertraline and Citalopram), Venlafaxine and Reboxetine on both platelet adhesion and plasma coagulation (activated partial thromboplastin time (APTT) and prothrombin time) . This study found that both SSRIs, but not Venlafaxine, significantly inhibited platelet adhesion to both collagen and fibrinogen in a concentration-dependent fashion. None of the drugs studied had a significant effect on plasma coagulation. 
* Reproductive system (pregnancy, de velopment and infancy) side effects
There has been ongoing controversy and uncertainty about the possible contribution of antidepressants to spontaneous abortion, pre-eclampsia, congenital malformations and neonatal development. But the majority of the studies concluded that only the Fluoxetine and Paroxetine should be avoided during the first trimester and in those at risk of unplanned pregnancy.  
* Musculoskeletal side effects
The most recent meta-analysis (237 studies), which pooled results from 13 qualifying cohort and case-control studies, found that SSRIs were associated with a significantly increased risk of fractures (RR51.72, 95% CI: 1.51-1.95, p < 0.001). This increased risk was also observed in studies that adjusted for depression (RR51.74, 95% CI: 1.28-2.36, p < 0.001) and for BMD (RR51.70, 95% CI: 1.28-2.25, p < 0.001) .
SEROTONIN AND NORADRENALINE REUPTAKE INHIBITORS (SNRIS)
* Cardiovascular side effects Serotonin-norepinephrine reuptake inhibitors (SNRIs) are associated with a small, but increased incidence of cardiovascular adverse events (hypertension, tachycardia and orthostatic hypotension), while at therapeutic doses they do not seem to cause QTc prolongation .
* Nervous system side effects Serotonin syndrome with rabdomiolysis occurred in a patient with Parkinson's disease after he had taken Venlafaxine 75 mg/ day for depression for two weeks . Previous reports of serotonin syndrome with Venlafaxine have been related to overdose . Parkinsonism or drug drug interactions with the antiparkinsonian medications may have predisposed this patient to serotonin syndrome at such low doses of Venlafaxine. Bruxism has been not infrequently associated with SSRIs, but there have been few reports associated with other antidepressants. Bruxism apparently related to Venlafaxine 150 mg/day has been reported in a 31-year-old woman after one week of treatment . She had experienced similar symptoms previously with the Escitalopram and Fluoxetine. The symptoms resolved with Buspirone 20 mg/day, and she was able to continue taking Venlafaxine.
* Reproductive system (pregnancy, development and infancy) side effects Galactorrhea and metrorrhagia have been attributed to Venlafaxine at therapeutic doses . There have been reports of neonatal withdrawal symptoms with SSRIs, but little is known of this phenomenon with other antidepressants. When seven mother-child pairs exposed to Venlafaxine from the second trimester, were studied , five of the neonates had a withdrawal syndrome, including tachypnea and respiratory distress; the changes corresponded to falling plasma Venlafaxine concentrations. The neonate exposed to the highest maternal dose of Venlafaxine (300 mg/day) had the most severe and most persistent signs. 
* Neurologic side effects
A study comparing somnolence determined by Asenapine, Olanzapine, Risperidone and Haloperidol relative to placebo evaluated ten clinical trials of patients with schizophrenia or bipolar disorder . The duration and incidence of somnolence was the greatest for Asenapine and Olanzapine (maximal for olanzapine) and with shorter time to onset than the other antipsychotics and placebo; patients with bipolar disorder were the most sensitive. 
Even if the second generation antipsychotics, compared with the first generation antipsychotics, carry a much lower risk to develop neurological symptoms, both classes can induce within hours of initiation of antipsychotic treatment, dystonic reactions, including torticollis, oculogyric crisis (upward deviation of the eyes) and lifethreatening laryngospasm, or after weeks of treatment they can induce rigidity, akinesia, bradykinesia, tremor and akathisia, symptoms that are collectively known as "extrapyramidal side-effects". 
A retrospective case analysis of 55 pediatric emergency department patients re ported presentations due to drug induced dystonic reactions with first generation of antipsychotics (Haloperidol, Chlorpromazine), second generation of antipsychotics (Risperidone) and antiemetics with antidopaminergic activity (Metoclopramide). 
A literature review identified Amisulpride, Flupenthixol, Haloperidol, Levopromazine, Sulpiride, Thioridazine, Zuclopenthixol and second generation antipsychotics at higher doses (Aripiprazole, Olanzapine, Risperidone) as high risk of inducing Parkinson symptoms.  Ziprasidone was identified as intermediate risk. 
* Metabolic and endocrine side effects
Most SGAs, and a part of FGAs, have been shown to cause weight gain and other metabolic syndromes, including dyslipidemia, and hyperglycemia (leading to type two diabetes mellitus). Specifically, dyslipidemia includes hypertriglyceridemia and low high-density lipoprotein levels. The SGAs are divided into high-Olanzapine, Clozapine, moderate-Quetiapine, Risperidone, and low-Ziprasidone, Aripiprazole risk classes for weight gain and metabolic side-effects according to a consensus statement by the American Diabetes Association and American Psychiatric Association in 2004. Possible mechanisms for weight gain include histaminic or serotonergic antagonism, or insulin resistance. Monitoring recommendations include measurement of waist circumference, fasting glucose, triglycerides, high density lipoprotein, and blood pressure routinely in patients taking SGAs (Nasrallah and Smeltzer, 2003; Rosenbaum et al., 2005; Marder and Wirshing, 2009).   Weight gain with SGAs typically occurs within the first four to twelve weeks of treatment and may or may not reach a plateau after one year .
Thus, an increase in the natural mortality rate of 1.5e2-fold as compared to the general population was reported for depressed, bipolar and schizophrenic patients (Brown, 1997; Harris & Barraclough, 1998; Joukamaa et al., 2001; Angst et al., 2002; Saha et al., 2007, Laursen et al., 2007)  which appears to be mainly due to an increased comorbidity for metabolic and cardiovascular illness that significantly worsens the incidence of mortality in this subpopulation. (Musselman et al., 1998; Osby et al., 2000; Cohn and Remington, 2003; McEvoy et al., 2005; Van der Kooy et al., 2007, Birkenaes et al., 2007). In addition, several studies reported a higher prevalence of metabolic syndrome in various psychotic disorders including bipolar and schizophrenic patients as compared to the general population (Birkenaes et al., 2007; Correll et al., 2008; Fiedorowicz et al., 2008; Sicras et al., 2008; Van Winkel et al., 2008), and this can be because of overweight or frank obesity, dyslipidemia, hypertension, hyperglycemia (impaired fasting glucose tolerance) but also smoking habits (Compton et al., 2006), poor diet and sedentary lifestyle (Brown et al., 1999). These are all aspects of medical concern which are predominant among individuals with major mental disorders. This legitimates the consideration of a cluster of factors identifiable as cardiometabolic disease risk (Newcomer, 2007). [48, 49]
A study of prolactin levels in 268 patients treated for schizophrenia with Olanzapine, Risperidone, Aripiprazole, Quetiapine or Perospirone in monotherapy found lower levels with Aripiprazole. [50, 51] Both Olanzapine and Risperidone were associated with higher levels as was female sex and higher dose  A study of 100 men with psychotic disorders found that the rate of sexual dysfunction was highest for Risperidone, followed by Trifluoperazine and Olanzapine, measured on three different scales . Rates of sexual function varied according to the scale used; decreased libido was the most prevalent except for orgasmic disorders for Risperidone on the ASEX scale. 
* Cardiovascular side effects
Many of the conventional antipsychotics have shown an increased risk in cardiac dysrhythmias, specifically with prolongation of the QRS or QTc intervals. This can lead to life-threatening ventricular arrhythmias such as torsade de pointes or ventricular fibrillation. The SGAs have prolonging effects on the QTc interval, much like some of the FGAs, but are often not clinically significant . A retrospective cohort study of elderly (over 65 years old) patients did not find that SGAs were associated with a significantly greater risk of cerebral-vascular events, cardiac arrhythmia and congestive heart failure compared to FGAs . Overall, there was a lower risk of mortality, but higher risk of myocardial infarction for SGAs compared to FGAs. 
* Gastrointestinal side effects
In the case of FGA anticholinergic side-effects lead to constipation, nausea, vomiting, and dry mouth. In severe cases, this can lead to paralytic ileus. Treatment should include regular use of stool softeners and bulking agents to promote regular bowel function. A rare hypersensitivity reaction has been described with the aliphatic phenothiazines, specifically Chlorpromazine. The incidence of cholestatic jaundice is approximately 0.1% and often develops in the first one or two months of treatment. Symptoms include nausea, fever, malaise, pruritus, abdominal pain, and jaundice, and signs include elevation of bilirubin and alkaline phosphatase (Nasrallahand Tandon, 2009) . For SGA transient elevation in liver enzymes may occur with Olanzapine early in treatment, but often resolves in nine or ten weeks. Anticholinergic effects with Olanzapine, Clozapine, and Quetiapine can result in constipation. 
* Reproductive system (pregnancy, de velopment and infancy) side effects
All SGAs are rated as category C by the FDA, which means there are few or no animal or human data to indicate absence of teratogenicity. Only Haloperidol, an older neuroleptic with 40 years of use, has been deemed safe in pregnancy, but its neurological side-effects to the mother and the fetus are a major drawback.
III. MOOD STABILIZERS
* Nervous System side effects
Tremor is a classic and common side effect caused by lithium, with an estimated rate of 27%. While usually benign, this adverse effect may lead to nonadherence or, in some cases, it may be an initial sign of lithium toxicity. Commonly, it presents in the hands or upper limbs at rest, oscillating at 8-12 Hz, and worsens during activity. Compiled results from a literature search on this side effect reveal that it usually manifests upon initiation of lithium, it is not progressive, and decreases over time. Other characteristics include its symmetric nature and correlation with dose. Its mechanism has never been closely examined but may be related to effects on brainstem serotonergic neurons.  
* Endocrine side effects Nephrogenic diabetes insipidus is a common adverse effect of lithium . Out of 56 patients who took lithium for an average of 11 years, 39 had urine volumes that exceeded three l/day, of whom 30 spontaneously reported polyuria and 35 reported that the polyuria had caused some dysfunction in their daily routine . The duration of psychiatric disorder, the duration of lithium treatment, and the total number of episodes, particularly depressive episodes, all correlated positively with the polyuria.
Major side effects of the chronic use of lithium medication also include hypothyroidism and goiter (Aral and Vecchio-Sadus, 2008; Grandjean and Aubry, 2009; Kibirige et al., 2013). A recent meta-analysis showed a 5.8 fold increase in the prevalence of clinical hypothyroidism among patients taking Lithium compared with those given placebo. Lithium treatment was also associated with increased levels of serum thyroid-stimulating hormone (TSH), calcium, and parathyroid hormone (McKnight et al., 2012). Consistent with these observations, alterations in thyroid function were also reported in populations consuming drinking water with high Lithium concentrations. 
* Cardiovascular side effects
Several cases of lithium related cardiotoxicity have been reported. These include a case of fatal sudden cardiac death ; sinus node dysfunction at therapeutic concentrations (0.94 and 1.06 mmol/l)  and moderately raised concentrations (2.32 mmol/l) ; and atrioventricular block at therapeutic concentrations in a patient who was also taking Clozapine . Two cases of Mobitz type II block
were associated with subtherapeutic lithium concentrations (0.4 and 0.2 mmol/l) , but since no information establishing possible causality was presented, it seems unlikely that lithium was causal in those cases. 
Of all the anticonvulsant mood stabilizers, the most used in psychiatry and with the most adverse effects is Valproic acid.
* Cardiovascular side effects
Very rarely, valproate-induced carnitine deficiency adversely affects cardiac function. Some studies attributed hypotension  and carotid artery intima media thickness to this treatment . One study measured carotid artery intima media thickness and serum lipids in 44 children with epilepsy taking Valproic Acid and 40 healthy children. Although there was no difference in serum lipid profiles, the intima media of the common carotid artery was significantly thicker in those who took valproic acid . This finding may be due to epilepsy and not to the drug.
* Gastrointestinal side effects
Gastrointestinal symptoms, such as nausea, anorexia, vomiting, gastritis, and diarrhea, occur in 36% of patients , although over 20% of them may be affected at high dosages . Stomatitis, parotid gland enlargement, and gingival hyperplasia are exceedingly rare   . In a retrospective survey, gastrointestinal adverse effects were less common in 150 patients taking valproate semisodium than in an equal number taking valproic acid 15 versus 29%), despite the fact that serum valproic acid concentrations were comparable in the two groups . Patients taking valproate semisodium were less likely
to discontinue medication because of gastrointestinal adverse effects (4 versus 13%). The difference was ascribed to the entericcoated formulation of valproate semisodium. The suggestion that Divalproex (valproate semisodium) causes fewer gastrointestinal adverse reactions than valproate  has been challenged . In other cited studies Divalproex was associated with a higher risk of gastrointestinal effects. 
* Reproductive system (pregnancy, development and infancy) side effects
A study found an association with Valproate exposure and the risk of developing autism spectrum disorder and childhood autism. The 14-year absolute risk is 1.53% (95% CI, 1.47-1.58%) for autism spectrum disorder and 0.48% (95% CI, 0.46 0.51 %) for childhood autism. Maternal valproate exposure was associated with a 2.9 fold increase (95% CI, 1.7-4.9) in autism spectrum disorder and a 5.2 fold increase (2.7-10.0) in childhood autism adjusted for multiple factors. This association was not found with other antiepileptics . A retrospective study reviewing fetal malformations and valproic exposure demonstrated a dose-dependent correlation and risk of abnormalities at birth. Spina bifida and hypospadias were associated with maternal exposure of 2 000 and 2 417 mg daily doses, respectively. Other malformations were associated with significant lower doses of 740-1 527 mg. Furthermore, mean maternal daily exposure decreased over time with a corresponding decrease in spina bifida and hypospadias, but not in other malformations. Of note, direct correlation cannot be inferred from the above findings. However, the authors did notice that the correlation may be stronger with spina bifida than hypospadias be cause 85% of spina bifida cases were associated with Valproic Acid  . A metaanalysis from pooled data looking at Valproic Acidum and various malformations by Jentink (2010) concluded that there was statistically significant evidence of associations between VPA exposure and spina bifida, atrial septal defect, cleft palate, hypospadias, polydactyly, and craniosynostosis. Similar significant associations were found by Vajda (2013) except in relation to cleft palate and hypospadias and by Werler (2011) in relation to neural tube defects, oral clefts, and hypospadias. Typically for Valproic Acid, there is primarily an up to 20 fold increased risk for spina bifida and other neural tube defects if the mother received treatment between the 17th and 28th day after conception (Dansky, 1991). This indicates that about 1-2% of exposed children will be affected. 
* Nervous system side effects
There have been several further reports of valproate induced hyperammonemic encephalopathy    . In one case, it was associated with central pontine mielinolysis and coma in a patient with Sjogren's syndrome who had taken long-term Valproic Acid for a psychiatric disorder . Encephalopathy has been studied in 63 adults who had taken Valproate for a minimum of at least two years in a retrospective analysis . Long duration of Valproate treatment did not correlate with the risk of encephalopathy. In seven cases, temporary administration of lactulose alone was effective and valproate was not withdrawn. The authors also concluded that this complication is relatively common. In one patient, there was a possible synergistic interaction of Valproic Acid and Topiramate with respect to the emergence of hyperammonemic encephalopathy . The authors speculated that inhibition of carbonic anhydrase by Topiramate might be the basis of this, since HCO is used in the synthesis of carbamoylphosphate in the urea cycle. In a young child, valproate-induced stupor was unusually associated with an electroencephalographic pattern of increased fast activity  . The authors speculated that this effect of valproate was related to an interaction of valproate with GABA metabolism and GABA neuronal networks. Tremor is seen in 15% of patients taking Valproate  , although its incidence can increase to over 60% at serum drug concentrations in a high range (80-150 mg/ml) ; it is clinically reminiscent of essential tremor and responds to dosage reduction. Asterixis has been associated with intoxication by most anticonvulsants, but with Valproate it can occur at therapeutic drug concentrations  .
* Metabolic side effects
Valproic acid can cause weight gain , insulin resistance, hypertriglyceridemia, and other components of metabolic syndrome . It decreases production of adiponectin, which is an adipocytokine that enhances insulin sensitivity . Valproic acid also increases the likelihood of PCO  , which is a syndrome of insulin resistance, obesity, infertility, and mood disorder. Slow release forms of Valproic acid may be more benign.
The effect of valproate on body weight and hormones has been studied in 52 healthy adults who were randomized to valproate or placebo in a double-blind protocol . Weight increased significantly with Valproate but not placebo. Those who took Valproate also had increased cravings for fast food and reduced glucose concentrations compared with placebo. Physical activity, hunger, binge eating, depression, and GLP-1 were increased by Valproate. The authors concluded that Valproate associated weight gain is probably due to reduced glucose concentrations and an increased motivation to eat in association with increased body size . Weight gain during Valproate treatment occurs during the first three months of therapy, and women are more susceptible than men. The mechanism is not known.
From the results of a systematic review of ten epidemiological studies, about 50% of patients would be expected to have significant weight gain during treatment for two or more years . The authors suggested that body weight should be measured before starting Valproate and that if body weight increases by two kg in the first consideration should be given to using another antiepileptic drug. 
Side effects can vary greatly among individual patients, not only depending on the doses, or on the medicine itself, but also because of the vulnerabilities that one can have. Polypharmacy, higher dosages and the treatments of those vulnerabilities can be associated with a great effect on the lifespan of the psychiatric patients.
Of course, a greater attention to the possible impact of the psychotropic medications on the physical health can aid clinicians in selecting appropriate treatments. The biggest effects on physical health are those caused by antipsychotics, followed by mood stabilizers, tricyclic antidepressants and newer antidepressants. Knowledge of these side effects, in tight balance with a well understanding of the patients' needs and vulnerabilities, will aid the full recovery of the psychiatric patients, without affecting the physical health. An appropriate management and monitoring strategy must be implemented also, with the sole objective to serve at the improving both the physical and the mental health of these generally disadvantaged populations.
ACKNOWLEDGMENTS AND DISCLOSURES
Authors state that there are no declared conflicts of interests regarding this paper.
[1.] Ziegler V.E., Taylor J.R., Wetzel R.D., Biggs J.T. Nortriptyline plasma levels and subjective side effects. Br J Psychiatry. 1978; 132(1): 55-6.
[2.] Reisby N., Gram LF., Bech P., Nagy A., Petersen G.O. et al. Imipramine: clinical effects and pharmacokinetic variability. Psychopharmacology (Berl). 1977; 54(3): 263-72.
[3.] Glassman A.H., Bigger J.T. Jr, Giardina E.V., Kantor S.J., Perel J.M., Lancet Davies M. Clinical characteristics of imipramine-induced orthostatic hypotension. 1979; 1(8114): 468-72.
[4.] Van Zwieten P.A. The central action of antihypertensive drugs, mediated via central alpha-receptors. J Pharm Pharmacol. 1973; 25(2): 89-95.
[5.] Meyler's Side Effects of Drugs (16th Edition) Tricyclic antidepressants. 2016,146-169.
[6.] Subramaniam M., Yuning A.S., Vaingankar J.A., Chong S.A. Cardiovascular Toxicity as a Result of Psychotropic Drugs. The Heart and Toxins. DOI: http://dx.doi.org/10.1016/B978-0-12-416595-3.00009-8. 2015. Elsevier Inc.
[7.] Greenberg H.E., Scharf S.M., Green H. Nortriptylineinduced depression of ventilatory control in a patient with chronic obstructive pulmonary disease. Am Rev Respir Dis. 1993; 147(5): 1303-5.
[8.] Sugarman P., Hughes T. Assault after ingestion of antidepressant. BMJ 1991; 303(6804): 720.
[9.] Fann W.E., Sullivan J.L., Richman B.W. Dyskinesias associated with tricyclic antidepressants. Br J Psychiatry. 1976; 128: 490-3.
[10.] Metabolic Syndrome and Psychiatric Illness: Interactions, Pathophysiology, Assessment and Treatment 2008 , cap 5.Academic Press.73-91.
[11.] Clarke I.M. Adynamic ileus and amitriptyline. Br Med J. 1971; 2(760): 531.
[12.] Martin-Merino E., Ruigomez A., Garcia Rodriguez L.A., Wallander M.A., Johansson S. Depression and treatment with antidepressants are associated with the development of gastro-esophageal reflux disease. Aliment Pharmacol Ther. 2010; 31(10): 1132-40.
[13.] Hunt K.A., Resnick M.P. Clomipramine-induced agranulocytosis and its treatment with G-CSF. Am J Psychiatry. 1993; 150(3): 522-3.
[14.] Taniguchi S., Hamada T. Photosensitivity and thrombocytopenia due to amitriptyline. Am J Hematol. 1996; 53(1): 49-50.
[15.] Albertini R.S., Penders T.M. Agranulocytosis associated with tricyclics. J Clin Psychiatry. 1978; 39(5): 483-5.
[16.] Kozakova M. Liekova purpura po antidepresivach. Drug induced purpura due to antidepressive drugs. Cesk Dermatol. 1971; 46(4): 158-60.
[17.] Vallada H.P., Gentil V. Musical hallucinations triggered by clomipramine? Br J Psychiatry. 1991; 159: 888-9.
[18.] Wehr T.A., Goodwin F.K. Can antidepressants cause mania and worsen the course of affective illness, Am J Psychiatry.1987; 144(11): 1403-11.
[19.] Wu C.S., Wang S.C., Cheng Y.C., Gau S.S. Association of cerebrovascular events with antidepressant use: a casecrossover study. Am J Psychiatry. 2011; 168(5): 511-21.
[20.] Puras P., Mitchell P.B. Side Effects of Drugs, Annual 35, Chapter 2, Antidepressant drugs, 2014. Elsevier B.V. 27-35.
[21.] Castro V.M., Clements C.C., Murphy S.N., Gainer V.S., Fava M, Weilburg J.B. et al. QT interval and antidepressant use: a cross sectional study On electronic health records. BMJ Clin Res Ed. 2013; 346:f288.
[22.] Smithson J., Mitchell P.B. Side Effects of Drugs Annual, Vol.36, Ch. 2, Antidepressant Drugs. 11-23. 2015. Elsevier B.V.
[23.] Smithson J., Mitchel P.B. Side Effects of Drugs Annual, Vol. 37, Ch. 2, Antidepressants, 15-28, 2015. Elsevier B.V.
[24.] Trenque T., Herlem E., Auriche P., Drame M. Serotonin reuptake inhibitors and hyperprolactinaemia: a case/non-case study in the French pharmacovigilance database. Drug Saf.2011; 34: 1161-6.
[25.] Lee Y.C., Shau W.Y., Chang C.H., Chen S.T., Lin M.S., Lai M.S. Antidepressant use and the risk of upper gastrointestinal bleeding in psychiatric patients: a nationwide cohort study in Taiwan. J Clin Psychopharmacol. 2012; 32(4):518-24.
[26.] Castro V.M., Gallagher P.J., Clements C.C., Murphy S.N., Gainer V.S., Fava M. et al. Incident user cohort study of risk for gastrointestinal bleed and stroke in individuals with major depressive disorder treated with antidepressants. BMJ Open. 2012; 2(2).
[27.] Palmsten K., Hernandez-Diaz S., Huybrechts K.F., Williams P.L., Michels K.B., Achtyes E.D. et al. Use of antidepressants near delivery and risk of postpartum hemorrhage: cohort study of low income women in the United States. BMJ Clin Res Ed. 2013; 347:f4877.
[28.] Van Walraven C., Mamdani M.M., Wells P.S., Williams J.I. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. BMJ Clin Res Ed. 2001; 323(7314):655-8.
[29.] Hackam D.G., Mrkobrada M. Selective serotonin reuptake inhibitors and brain hemorrhage: a meta-analysis. Neurology 2012; 79(18):1862-5.
[30.] Hallback I., Hagg S., Eriksson A.C., Whiss P.A. In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation. Pharmacol Rep. 2012; 64(4):979-83.
[31.] Smithson J., Mitchell P.B. Side Effects of Drugs Annual, Vol.36, Ch. 2, Antidepressant Drugs,11-23.
[32.] Grigoriadis S., Vonder Porten E.H., Mamisashvili L., Roerecke M., Rehm J., Dennis C.L. et al. Antidepressant exposure during pregnancy and congenital malformations: is there an association? A systematic review and metaanalysis of the best evidence. J Clin Psychiatry. 2013; 74(4):e293-308.
[33.] Myles N., Newall H., Ward H., Large M. Systematic meta-analysis of individual selective serotonin reuptake inhibitor medications and congenital malformations. Aust N Z J Psychiatry. 2013; 47(11):1002-12.
[34.] Correll C.U., Detraux J., De Lepeleire J., De Hert M. Effects of antipsychotics, antidepressants and mood stabilizers on risk for physical diseases in people with schizophrenia, depression and bipolar disorder. World Psy. 2015; 14:119-136.
[35.] Rajapakse S., Abeynaike L., Wickramarathne T. Venlafaxine-associated serotonin syndrome causing severe rhabdomyolysis and acute renal failure in a patient with idiopathic Parkinson disease. J Clin Psychopharmacol. 2010; 30(5): 620-2.
[36.] Wilson A.D., Howell C., Waring W.S. Venlafaxine ingestion is associated with rhabdomyolysis in adults: a case series. J Toxicol Sci. 2007; 32: 97-101.
[37.] Kuloglu M., Ekinci O., Caykoylu A. Venlafaxine associated nocturnal bruxism in a depressive patient successfully treated with Buspirone. J Psychopharmacol. 2010; 24(4): 627-8.
[38.] Berilgen M.S. Late-onset galactorrhea and menometrorrhagia with venlafaxine use in a migraine patient. J Clin Psychopharmacol. 2010; 30(6): 753-4.
[39.] Boucher N., Koren G., Beaulac-Baillargeon L. Maternal use of venlafaxine near term: correlation between neonatal effects and plasma concentrations. Ther Drug Monit. 2009; 31 (3): 404-9.
[40.] Chan H.N.,. Mitchell P.B Side Effects of Drugs, Vol. 34, ch. 2, Antidepressant drugs, 17-23 in J.K. Aronson (Editor), 2012. Elsevier B.V.
[41.] Gao K., Mackle M., Cazorla P., Zhao J., Szegedi A. Comparison of somnolence associated with asenapine, olanzapine, risperidone, and haloperidol relative to placebo in patients with schizophrenia or bipolar disorder. Neuropsychiatr Dis Treat. 2013; 9:1145-57.
[42.] Chue P., Neagu B. Side Effects of Drugs. Vol. 36, Ch. 6, Antipsychotic Drugs.
[43.] Schlaepfer T.E, Nemeroff C.B. Handbook of Clinical Neurology, Vol. 106 (3rd series) Neurobiology of Psychiatric Disorders, Ch.39, Antipsychotic drugs, 657-667.
[44.] Derinoz O., Caglar A.A. Drug-induced movement disorders in children at pediatric emergency department: 'dystonia'. Emerg Med J. 2013; 30(2):130-3.
[45.] Manage drug-induced parkinsonism through early recognition of the condition and discontinuation of the causative agent. Drugs Ther Perspect. 2012; 28(12):20-3.
[46.] Yumru M.,. Savas H.A, Kurt E., Kaya M. C., Selek S. et al. Research report: Atypical antipsychotics related metabolic syndrome in bipolar patients. J of Affect Disord. 98. 2007. 247-252.
[47.] Arterburn D., Wood G. C., Theis M.K., Westbrook E.O., Anau J. et al. Obesity Research & Clinical Practice Antipsychotic medications and extreme weight gain in two health systems, Elsevier. 2015.
[48.] Coccurello R., Moles A. Potential mechanisms of atypical antipsychotic-induced metabolic derangement: Clues for understanding obesity and novel drug design. Pharmacology and Therapeutics. 2010. 210-252.
[49.] Choong E., Bondolfi G., Etter M., Jermann F., Aubry J.M. et al. Psychotropic drug-induced weight gain and other metabolic complications in a Swiss psychiatric population. J of Psych Research 46.2012. 540-548.
[50.] Hasnaina M., Vieweg W.V.R., Fredrickson S.K., Brooks M. B., Fernandez A. et al. Clinical monitoring and management of the metabolic syndrome in patients receiving atypical antipsychotic medications. Primary care diabetes 3.2009. 5-15.
[51.] Suzuki Y., Sugai .T, Fukui N., Watanabe J., Ono S., Tsuneyama N. et al. Differences in plasma prolactin levels in patients with schizophrenia treated on monotherapy with five second-generation antipsychotics. Schizophr Res. 2013; 145(1-3):116-9.
[52.] Nebhinani N., Grover S., Avasthi A. Sexual dysfunction in male subjects receiving trifluoperazine, risperidone, or olanzapine: rates vary with assessment questionnaire. Prim Care Companion CNS Disord. 2012; 14(2).
[53.] Vasilyeva I., Biscontri R.G., Enns M.W., Metge C.J., Alessi-Severini S. Adverse events in elderly users of antipsychotic pharmacotherapy in the province of Manitoba: a retrospective cohort study. J Clin Psychopharmacol. 2013; 33(1):24-30.
[54.] Thomas R.S., Mei T.L., Megan E. M. Side Effects of Drugs Annual, Vol.37,Ch.3, Lithium, pg. 33-45.
[55.] Baek J.H., Kinrys G., Nierenberg A.A. Lithium tremor revisited: pathophysiology and treatment. Acta Psychiatr Scand. 2014; 129(1):17-23.
[56.] Trepiccione F., Christensen B.M. Lithium induced nephrogenic diabetes insipidus: new clinical and experimental findings. J Nephrol. 2010; 23(Suppl 16): S43-8.
[57.] Pradhan B.K., Chakrabarti S., Irpati A.S., Bhardwaj R. Distress due to lithium induced polyuria: exploratory study. Psychiatry Clin Neurosci. 2011; 65: 386-8.
[58.] Alfred B. Handbook on the Toxicology of Metals 4E, Ch.44, Lithium. 2015. 969-975.
[59.] Venkatarathnamma P.N., Patil A.R., Nanjundaiah N. Fatal lithium toxicity with therapeutic levels-a case report. Int J Clin Pharmacol Ther. 2011; 49(5): 336-8.
[60.] Singh L.K., Praharaj K., Munda S.K., Khess C.R.J. Lithium-induced sinus node dysfunction at therapeutic serum levels. Natl Med J India. 2011; 24(3): 151-2.
[61.] Martinez J.A., Sousa D.R., Portero J.N., Martinez A.M. Sinus node dysfunction due to lithium intoxication. Rev Exp Cardiol. 2011; 64(3): 243-50.
[62.] Gabeler E.E., van Miltenburg A.J.M. Complete AV-block secondary to lithium clozapine therapy and relapsing multiple sclerosis in a bipolar patient. BMJ Case Rep. 2011.
[63.] Armstrong E.J., Dubey A., Scheinman M.M., Badhawar N. Lithium-associated Mobitz II block: case series and review of the literature. Pacing Clin Electrophysiol. 2011; 34(5): e47-51.
[64.] El-Mallakh R.S., Roberts R. J., Yonglin G., Aronson J.K. (Ed.) Side Effects of Drugs, Annual 35. Chapter 3, Lithium, pg. 41-55.
[65.] White J.R., Santos C.S. Intravenous valproate associated with significant hypotension in the treatment of status epilepticus. J Child Neurol. 1999; 14(12): 822-3.
[66.] Erdemir A., Cullu N., Yis U., Demircioglu F., Kir M. et al. Evaluation of serum lipids and carotid artery intima media thickness in epileptic children treated with valproic acid. Brain Dev. 2009; 31(10): 713-6.
[67.] Sleiman C., Raffy O., Roue C., Mal H. Fatal pulmonary hemorrhage during high-dose valproate monotherapy, Chest. 2000; 117(2): 613.
[68.] Beydoun A., Sackellares J.C., Shu V. Safety and efficacy of divalproex sodium monotherapy in partial epilepsy: a double-blind, concentration-response design clinical trial. Depakote Monotherapy for Partial Seizures Study Group. Neurology. 1997; 48(1): 182-8.
[69.] Syrjanen S.M., Syrjanen K.J. Hyperplastic gingivitis in a child receiving sodium valproate treatment. Proc Finn Dent Soc. 1979; 75(5-6): 95-8.
[70.] Reisser C., Maier H. Sialaden dose durch Valproat dauermedikation. Sialadenosis caused long-term Valproate medication. Laryngorhinootologie. 1991; 70(7): 384-6.
[71.] Behari M. Gingival hyperplasia due to sodium valproate. J Neurol Neurosurg Psychiatry. 1991; 54(3): 279-80.
[72.] Zarate C.A. Jr., Tohen M., Narendran R., Tomassini E.C., McDonald J. et al. The adverse effect profile and efficacy of divalproex sodium compared with valproic acid: a pharmacoepidemiology study. J Clin Psychiatry. 1999; 60(4): 232-6.
[73.] Levine J., Chengappa K.N., Parepally H. Side effect profile of enteric-coated divalproex sodium versus valproic acid. J Clin Psychiatry. 2000; 61(9): 680-1.
[74.] Wagner P.G., Welton S.R., Hammond C.M. Gastrointestinal adverse effects with divalproex sodium and valproic acid. J Clin Psychiatry. 2000; 61(4): 302-3.
[75.] Meyler's Side Effects of Drugs (16th Edition). 2016. p. 303-337.
[76.] Christensen J., Gronborg T.K., Sorensen M.J. et al. Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism. JAMA. 2013; 309:1696-703.
[77.] Vajda F.J. Effect of anti-epileptic drug therapy on the unborn child. J Clin Neurosci. 2014; 21:716-21.
[78.] Spoelhof B., Frendak L., Lara L.R. Side Effects of Drugs Annual, Vol. 37, Ch. 7, Antiepileptics, pg. 85-107.
[79.] Chambers C., Schaefer C. Drugs During Pregnancy and Lactation. Epilepsy and antiepileptic medications, Ch. 2.10, 2015. Elsevier B.V.
[80.] Jamrozinski K., Gruber O., Kemmer C., Falkai P., Scherk H. Neurocognitive functions in euthymic bipolar patients. Acta Psychiatr Scand. 2009; 119(5): 365-74.
[81.] Goswami U., Sharma A., Varma A., Gulrajani C., Ferrier I.N. et al.The neurocognitive performance of drug free and medicated euthymic bipolar patients do not differ. Acta Psychiatr Scand. 2009; 120(6): 456-63.
[82.] Holmes M.K., Erickson K., Luckenbaugh D.A., Drevets W.C., Bain E.E. et al. A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression. Bipolar Disord. 2008; 10(7): 806-15.
[83.] Wingo A.P., Wingo T.S., Harvey P.D., Baldessarini R.J. Effects of lithium on cognitive performance: a metaanalysis. J Clin Psychiatry. 2009; 70(11): 1588-97.
[84.] Phillips B.D., Gopalakrishnan G., Gohh R., Hennessey J.V. Lithium toxicity precipitated by profound hypothyroidism. Thyroid. 2008; 18(6): 651-4.
[85.] van Hoek I., Daminet S. Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review. Gen Comp Endocrinol. 2009; 160(3): 205-15.
[86.] Gershengorn M.C., Izumi M., Robbins J. Use of lithium as an adjunct to radioiodine therapy of thyroid carcinoma. J Clin Endocrinol Metab. 1976; 42(1): 105-11.
[87.] Camacho C.P., Latini F.R., Oler G., Hojaij F.C., Maciel R.M. et al. Down regulation of NR4A1 in follicular thyroid carcinomas is restored following lithium treatment. Clin Endocrionol (Oxf). 2009; 70(3): 475-83.
[88.] Focosi D., Azzara A., Kast R.E., Carulli G., Petrini M. Lithium and hematology: established and proposed uses. J Leukocyte Biol. 2009; 85(1): 20-8.
[89.] Brunoni A.R., Ferreira L.R.K, Gallucci-Neto J., Xanetti M.V. Lithium as a treatment of clozapine-induced neutropenia: a case report. Prog Neuropsychopharmacol Biol Psychiatry. 2008; 32: 2006-7.
[90.] Daneshmand A., Rahimian R., Mohammadi H., Ejtemaee-Mehr S., Tavangar S.M. et al. Protective effects of lithium on acetic acid-induced colitis in rats. Dig Dis Sci. 2009; 54(9): 1901-7.
[91.] Malhi G.S., Mitchell P.B., Caterson, I., "Why getting fat, Doc?' Weight gain and psychotropic medications. Aust. N.Z J. Psychiatry. 2001; 35:315-321.
[92.] Pylvanen V. et al. Insulin-related metabolic changes during treatment with valproate in patients with epilepsy. Epilepsy Behav. 2006; 8:643-648.
[93.] Qiao L., Schaack J., Shao J. Suppression of adiponectin gene expression by histone deacetylase inhibitor valproic acid. Endocrinology. 2006; 147:865-874.
[94.] Isojarvi J.I. et al. Altered ovarian function and cardiovascular risk factors in valproate treated women. Am. J. Med. 2001; 111:290-296.
[95.] Martin C.K., Han H., Anton S.D., Greenway F.L., Smith S.R. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol. 2009; 23(7): 814-25.
[96.] Masuccio F., Verrotti A., Chiavaroli V., de Giorgis T., Giannini C. et al. Weight gain and insulin resistance in children treated with valproate: the influence of time. J Child Neurol. 2010; 25(8): 941-7.
[97.] Verrotti A., D'Egidio C., Mohn A., Coppola G., Chiarelli F. Weight gain following treatment with valproic acid: pathogenetic mechanisms and clinical implications. Obes Rev. 2011; 12(5): e32-43.
Alexandra BOLOS-M. D., Ph. D., Senior Psychiatrist, Lecturer, "Gr. T. Popa" University of Medicine and Pharmacy Iasi, Romania
Dumitrita GAFENCU-SAVLOVSCHI-M. D., Resident Physician in Gastroenterology, Institute of Gastroenterology Iasi, Romania
Andreea Silvana SZALONTAY-M. D., Ph. D., Senior Psychiatrist, Lecturer, "Gr. T. Popa" University of Medicine and Pharmacy Iasi, Romania
M. D., Resident Physician in Gastroenterology Institute of Gastroenterology and Hepathology, "Sf. Spiridon" Hospital, No. 1 Bd. Independentei, zip code 700111, Iasi, Romania E-mail: email@example.com
Submission: April, 23rd, 2016
Acceptance: May, 16th, 2016
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|Author:||Bolos, Alexandra; Gafencu-Savlovschi, Dumitrita; Szalontay, Andreea Silvana|
|Publication:||Bulletin of Integrative Psychiatry|
|Date:||Jun 1, 2016|
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