Pathways to Substance Use and Abuse

Neuroscience medicine clinicians encounter patients every day who have both a mental and substance use disorder.

This co-occurrence, or comorbidity, complicates diagnosis, treatment and outcome.

The exact mechanism for this comorbidity issue is unclear.

A recent study out of Washington University in St. Louis and King's College London provides some insight into this comorbidity issue.

They examined participants in the Study of Addiction: Genetics and Environment (SAGE). These subjects provided genetic samples and psychiatric interviews to the research team.

Five psychiatric disorders were studied including attention deficit hyperactivity, autism spectrum disorder, major depression, bipolar disorder and schizophrenia. A initial finding ruled out any link between genetic risk for autism spectrum disorder and any substance use/abuse risk.

The remaining four psychiatric disorders did increase risk for substance use and abuse in a general manner. This means genetic risk for ADHD, bipolar disorder, major depression and schizophrenia all contribute to a general risk for substance use/abuse across all drug categories.

Additionally, the team reported some specific drug use/abuse with individual genetic risk for ADHD, bipolar disorder, major depression and schizophrenia. These specific pathways included:

• Major depression polygenetic risk score and non-problem cannabis use
• Major depression polygenetic risk score and severe cocaine dependence
• Schizophrenia polygenetic risk score and  non-problem cannabis use and severe cannabis dependence
• Schizophrenia polygenetic risk score and severe cocaine dependence

The take-home message from this study is that genetic risk for many psychiatric disorders also contributes to a increased risk for general substance use/abuse. Additionally, some psychiatric disorders appear to increase risk for specific substance use/abuse issues.

Prevention, assessment and treatment services need to address this relationship and the needs for each component of illness in those with comorbidity.

Individuals with more interest in this topic can access the free full-text manuscript by clicking on the link in the citation below.

Follow me on Twitter WRY999

Image is an original graphic produced by me based on content in the manuscript.

Carey CE, Agrawal A, Bucholz KK, Hartz SM, Lynskey MT, Nelson EC, Bierut LJ, & Bogdan R (2016). Associations between Polygenic Risk for Psychiatric Disorders and Substance Involvement. Frontiers in genetics, 7 PMID: 27574527

Preventing Depression Following Brain Injury

Depression is a common feature following traumatic brain injury (TBI). Post-TBI depression may be difficult to treat and evolve into a chronic depression syndrome.

A recent published study demonstrates that prophylactic SSRI antidepressant treatment may reduce the incidence of depression following TBI.

This study was conducted by investigators affiliated with Baylor College of Medicine and the Department of Psychiatry at the University of Iowa.

Ninety four subjects were recruited to this randomized control trial.

Active drug treatment was provided by the selective serotonin reuptake inhibitor sertraline. Subjects were dosed up to 100 mg per day of sertraline and followed for 24 weeks.

The primary findings of the study included the following:

• Sertraline was well-tolerated with few adverse events in the study population
• By 24 weeks approximately 25% of control subjects met criteria for depression while only about 7% of sertraline subjects met criteria for depression
• The number of subjects needed to treat to prevent one person developing depression post-TBI was 5.9

The authors note in the discussion that sertraline and the SSRI class may be linked to:

"enhanced neuroplasticity in mood regulation areas, such as the hippocampus and prefrontal cortex"

The authors had previously noted an enhanced neuropsychological performance following TBI with the SSRI escitalopram. They were unable to replicate that finding in the current study.

This is an important study that deserves wider replication. If confirmed, SSRI primary prevention of depression following TBI may become a common practice.

Follow me on Twitter WRY999

Photo of monarch butterfly depositing egg on milkweed plant is from the author's files.

Jorge RE, Acion L, Burin DI, & Robinson RG (2016). Sertraline for Preventing Mood Disorders Following Traumatic Brain Injury: A Randomized Clinical Trial. JAMA psychiatry PMID: 27626622

Genetics of Depression: Secondary Markers

In my previous post, I highlighted a recent study of genetics and major depression from the 23andMe database.

I have had a chance to review this manuscript in more detail. One of the findings of interest involved secondary marker or secondary phenotypes.

Fifteen genetic loci were identified in this 23andMe sample using a discovery and replication data set.

Secondary phenotypes with the highest correlation with the 17 SNPs identified in the study included (effect) :

• Taking a selective serotonin reuptake inhibitor (SSRI) (.448)
• Any medication for mental health reasons (.421)
• Self-reported anxiety (.323)
• Self-reported panic attacks (.319)
• Early age of onset depression (.283)
• Insomnia (.272)
• Prescription pain medication (.236)
• Obesity with BMI>30 (.216)
• Overweight BMI >27 (.212)

The research team was able to identify one SNP (rs12552 in the OLFM4 or olfactomedin 4 region) that correlated with reporting of panic attacks, use of medication for mental health, pain, insomnia problems, BMI >27 and early age of onset of depression.

This study supports use of self-report of depression diagnosis or treatment of depression for genetic studies. Such approaches may open large data sets for understanding the genetics of neuroscience medicine disorders like depression.

Click on the PMID link to access the study abstract.

Follow me on Twitter WRY999

Photo of fisherman at sunset is from my files.

Hyde CL, Nagle MW, Tian C, Chen X, Paciga SA, Wendland JR, Tung JY, Hinds DA, Perlis RH, & Winslow AR (2016). Identification of 15 genetic loci associated with risk of major depression in individuals of European descent. Nature genetics PMID: 27479909

Genetics Leading to Better Bipolar Disorder Diagnosis

I wanted to alert Brain Posts readers to an important new review of genetics and diagnosis in brain disorders including bipolar disorder.

One hope for the emerging genetics research in mental disorders is a better diagnostic classification system.

The current psychiatric diagnostic system is hampered by use of a primary symptoms and signs approach leading to messy heterogeneous groups of clinical conditions.

Elliot Gerson has been a giant in neuroscience genetics for quite some time and recently published an important manuscript titled: "Genetic and genomic analyses as a basis for new diagnostic nosologies" in the journal Dialogues in Clinical Neuroscience.

Gershon notes current clinical diagnostic categories in psychiatry fail three of five tests for diagnostic validity described by Feigher in 1972:

• family study clustering
• course of illness 
• laboratory tests

There is promise for using genetic and genomic findings to improve diagnostic validity in psychiatric disorders. Gershon goes on to outline what is currently known in psychiatric genetics and how future genetic research can lead to "biologically coherent diagnostic entities".

Here is my summary on what I see as the key points in the review:

• The number of common gene single-neucleotide polymorphisms (SNPs) linked to brain disorders is growing (from 10 to over 100 for schizophrenia an example)
• Summing risk across known schizophrenia SNPs using risk profile scores accounts for 7% of genetic variance in schizophrenia (this increases to up to 23% of variance when broader phenotypic systems are used)
• A similar SNP risk profile approach separates bipolar disorder groups from controls
• Larger sample sizes may increase this SNP genetic variance understanding in schizophrenia and bipolar disorder
• Some SNPs contribute to risk for more than one disorder i.e. schizophrenia, bipolar disorder and major depression showing weakness of current classification system
• Common genome-wide SNP data may be a promising path to defining better diagnostic categories
• Rare variants such as copy number variations (CNVs) may also be promising for improved psychiatric diagnosis
• Chromosome 22q11 deletion (DiGeorge syndrome or velocardiofacial syndrome) occurs in 1/4000 births and has high penetrance for psychiatric diagnosis although nonspecific (23% autism sprectrum, 68% schizophrenia, 26% bipolar disorder)
• Brain molecular network modeling also holds promise as a basis for diagnosis
• Many known risk genes for psychiatric illness have been linked to key brain network nodes
• Genetic variants could be mapped to human molecular networks and this map may lead to predictable "therapeutic targets"
• Brain connectivity networks (fMRI) may be a promising alternate approach to psychiatric diagnosis

The validity criteria for psychiatric diagnosis described by Feighner in 1972 continue to be a gold standard. Emerging genetic, genomic and brain connectivity research may be part of the tool set that has been missing. Applying these tools to better diagnosis holds promise for new and better treatment and the reduction in pain and suffering for many brain disorders.

Interested readers can access the free full-text manuscript of the Gerson and Grennan review by clicking on the PMID link in the citation below.

Photo of brown pelican and ruddy turnstone is from the author's files.

Follow the author on Twitter WRY999

Gershon ES, & Grennan KS (2015). Genetic and genomic analyses as a basis for new diagnostic nosologies. Dialogues in clinical neuroscience, 17 (1), 69-78 PMID: 25987865

Male Depression Risk Via Childhood Conduct Disorder

Conduct disorder represents an important childhood-onset condition that commonly persists into adulthood.

Adult antisocial personality disorder and substance abuse are known risks associated with conduct disorder.

A recent study by Kenneth Kendler and Charles Gardner identified male conduct disorder as a risk factor for adult major depression.

Their study using the Virginia Twin Registry examined 20 developmental risk factors in male and female twins for presence of recent adult major depression.

A key finding in their study was gender specificity for several of the developmental risk factors. Many of the developmental risk factors increased risk for later depression in both males and females.

However, several developmental risk factors showed a predominant effect in males. These male predominant risk factors included the following variables:

• Conduct disorder
• History of childhood sexual abuse
• Drug abuse
• Past major depression
• Stressful life events

Conduct disorder and presence of drug abuse were classified as having moderate effect size in male gender predominance.

Specific types of stressful life events were noted to have a strong male predominance. Stressful life events that included financial loss, occupational difficulty and legal problems were more commonly found in the male twins with depression.

The authors note:

"Our results with externalizing psychopathology are consistent with a wide range of studies finding that men have higher rates of conduct disorder and drug abuse and that both of these disorders are associated with a higher risk for major depression."

The take home message for clinicians is that assessment of childhood conduct disorder is important in children, adolescents and adults. In adult males, childhood conduct disorder represents an important risk factor for adult major depression.

Readers with more interest in this research can access the free full-text abstract and manuscript by clicking on the DOI link in the citation below.

Photo of electus parrot pair is from the author's files.

Follow the author on Twitter @WRY999

Kendler, K., & Gardner, C. (2014). Sex Differences in the Pathways to Major Depression: A Study of Opposite-Sex Twin Pairs American Journal of Psychiatry, 171 (4), 426-435 DOI: 10.1176/appi.ajp.2013.13101375

Conduct Disorder Research Links: II

Here are some additional links to important recent research in conduct disorder.

Click on the title to be directed to the abstract. Many of the abstracts also have links to the free full-text manuscripts.

Age of onset for CD

This twin study examined the correlates of childhood versus adolescent onset conduct disorder. Both types showed a strong genetic influence (62% and 65%). Childhood onset CD was strongly linked to adult antisocial behavior while adolescent onset CD was not. A specific genetic factor was felt to contribute to a combined CD/ADHD phenotype.

Sex difference in pathway to major depression

Twenty developmental risk factors were examined for contribution to later major depression in a series of opposite-sex twins. The authors identified conduct disorder as a stronger predictor of depression in males. Financial, legal and occupational life events also uniquely contributed a strong influence for depression risk in men.

Conduct disorder and evoked auditory P300 brain waves

This study looked at an evoked brain wave potential (known as the P300) as a biomarker for conduct disorder risk. Reduced P300 amplitude was linked to conduct disorder symptoms. Both reduced P300 and conduct disorder appeared related to a genetic contribution.

Brain structure and adolescent disruptive behavior disorder

A group of adults adolescents with externalizing disorders were compared to a control group using MRI and diffusion tensor imaging. Disruptive behavior disorder was linked to delayed white matter maturation in the corpus callosum and superior longitudinal fasciculus.

Reduced cortical surface area in adolescents with conduct disorder

This study found a reduced cortical volume and cortical surface area in the brain prefrontal cortex of adolescents with a conduct disorder diagnosis. They note these findings may help identify neurodevelopmental mechanisms in the disorder.

Early intervention effects on psychopathology, crime and well-being

Kindergartners in this study were screened for conduct disorder and randomly assigned to a 10-year intervention versus control. At 25 years of age, the intervention group had a lower rate of and psychiatric disorder 59% versus 69%. Intervention subjects also had lower scores on violent and drug crime behavior. Another study using this cohort found lower scores on adolescent conduct disorder and oppositional defiant disorder compared to controls.

Photo of entry to Dingle Bay in Ireland is from the author's files.

Follow the author on Twitter @WRY999.

Brain Volume Differences in ADHD Normalize By Adulthood

Brain volume differences in ADHD have been documented in some childhood studies.

ADHD symptoms diminish with maturation in many but not all individuals. It is unclear whether this improvement in symptoms is also related to maturation of brain regions.

A recent study from the Netherlands provides some answers on this issue. A. Marten H. Onnink and colleagues performed a structural MRI study of 119 adults with ADHD compared to a group of controls.

This study is important because it examined effects of gender, comorbid depression and treatment history on key brain regions including the basal ganglia, amygdala and hippocampus.

The key findings from this study include the following:

• Women with adult ADHD showed no differences from controls on brain volume measures
• Men with adult ADHD showed reduced right caudate volumes and these volumes were negatively correlated with current hyperactivity symptom scores
• Comorbid major depression in adult ADHD was linked to smaller hippocampus volumes. ADHD without a history of depression was not linked to any differences in hippocampal volumes

A history of major depression in ADHD subjects was common (37% of men and 52% of women). Additionally, this sample high rates of current stimulant use (69% of the sample).

The authors note their study found essentially no link between adult ADHD and brain volumes. The only exception was the finding of reduced right caudate volumes in men with ADHD. 

The authors also note:

"Although male and female adults with ADHD have similar phenotypic features in terms of symptom rating and comorbidity patterns, the gender-specific finding for caudate nucleus volume suggests that partially distinct neurobiological deficits underlie ADHD in males and females."

Structural brain measures are only one element of brain imaging in ADHD and other disorders. In my previous posts, I reviewed studies linking ADHD with functional connectivity (white matter) deficits in both children and adults.

Studies of neural networks in ADHD continue to be an important area for future research. Understanding network abnormalities will be key in understanding the pathophysiology of the disorder.

Readers with more interest in this topic can access the free full text manuscript by clicking on the PMID link in the citation below.

Figure is from a screen shot of the basal ganglia from the iPad app 3D Brain. It illustrates the brain caudate region found to be reduced in adult men but not women with ADHD.

Follow the author on Twitter @WRY999.

Onnink AM, Zwiers MP, Hoogman M, Mostert JC, Kan CC, Buitelaar J, & Franke B (2014). Brain alterations in adult ADHD: effects of gender, treatment and comorbid depression. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology, 24 (3), 397-409 PMID: 24345721

Topiramate Augmentation in Major Depression

Molecular Model of the Drug Topiramate

Currently available antidepressants provide significant relief from major depression in many patients.  However, a significant number of patients receive little or limited relief following an initial trial of a standard first-line drug from the selective serotonin re-uptake inhibitor class of agents.


A common clinical strategy after initial drug non-response and non-remission is to consider pharmacological augmentation.  Augmentation options for clinicians include lithium carbonate, triiodthyronine (thyroid hormone), a second antidepressant, an atypical antipsychotic or adding psychotherapy if it is not already being provided.


Despite the number and range of augmentation options, additional options need to be explored given the persistence of depressive symptoms in many individuals.  A small study from Iran suggests one alternative to consider may be the drug topiramate.


Topiramate is a drug approved by the FDA for the treatment of epilepsy and migraine headaches  in the United States.  It is not approved for the treatment of any primary psychiatric disorder.  The exact mechanism of action for topiramate is unknown although it is known to have effects on the sodium channel, gamma-amino butyric acid (GABA) receptors, glutamate receptors and act as a carbonic anhydrase inhibitor.


Mowla and Kardeh have published a small study of 42 subjects randomized to topiramate or placebo.  The key elements of the study include:

• Subjects: Adults with DSM-IV major depressive disorder who had failed to respond to eight weeks of treatment with an SSRI drug (fluoxetine, citalopram or sertraline)
• Drug: Topiramate 25 mg per day increased by 25 mg per week throughout the trial (mean dosage 175 mg/day) or placebo
• Clinical trial design: Double-blind, randomized controlled trial with primary outcome measure the Hamilton Depression Rating scale (HAM-D) administered by a psychologist not involved in treatment

Fifty three subjects started the study with 11 dropouts (six in the topiramate group and five in the placebo group).  HAM-D scores statistically decreased more in the topiramate group (21.6 at baseline to 14.7 at 8 weeks) than in the placebo group (21.9 at baseline to 20.8 at 8 weeks).


Since a score of seven or more is considered remission in MDD, the mean score of 14.7 in the topiramate groups suggests significant residual symptomatology.  The authors do not provide the number of subjects meeting remission criteria in the topiramate and placebo groups by 8 weeks.


Nevertheless, topiramate has some potential significant advantages in the treatment-resistant major depression population.  First, it is a generic drug and would have some cost advantages in comparison to some of the other options.  Second, topiramate it typically weight neutral or produces a slight weight reduction.  Most antidepressants increase weight over time so this might be an important advantage.  Third, topiramate might hold an advantage in treatment of MDD populations with migraine or epilepsy--disorders with an indication for the drug.


This study is too small to change clinical practice patterns or guidelines.  Additional larger replication studies need to be considered.  

Molecular model of the drug topiramate from Wikipedia Creative Commons file released to the public domain.  Author of the model is: Fvansconsellos

Mowla A, & Kardeh E (2011). Topiramate augmentation in patients with resistant major depressive disorder: a double-blind placebo-controlled clinical trial. Progress in neuro-psychopharmacology & biological psychiatry, 35 (4), 970-3 PMID: 21291943

Inflammation, Depression and Heart Disease

Sunset in Santa Fe, New Mexico

Major depression appears linked to risk for coronary artery disease and an adverse outcome following myocardial infarction.  The mechanism for this association is unclear.

One proposed mechanism relates to systemic markers of inflammation.  Elevated serum blood levels of inflammatory markers such as interleukin-6 and C-reactive protein are risk factors for heart disease.  Some research point to higher inflammatory markers levels in samples of individuals with depression.

Duivis and colleagues from the Netherlands and the United States recently published an informative study on this issue in the American Journal of Psychiatry.  Their study prospectively examined a series of patients with heart disease with measurements of depression and markers of inflammation.  The key elements of the design of their study included:

Subjects: 667 individuals with documented coronary artery disease interviewed yearly for 5 years
Depression Assessment: 9-item Patient Health Questionnaire corresponding to the 9 items making up the criteria for major depression in DSM-IV.  Subjects were grouped into three categories: never scoring 10 or more on the PHQ, scoring 10 or more at one time, scoring 10 or more at 2 or more interviews
Inflammatory Markers: Fasting blood samples measured for high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6) and fibrinogen.

Subjects with two or more periods with significant depressive symptoms showed statistically higher levels of hsCRP and IL-6 than the other two subject groups (fibrinogen levels showed a trend for higher levels, p=.06)

Subjects with two or more periods with significant depressive symptoms tended to be younger, have a diagnosis of myocardial infarction, use aspirin daily and have lower levels of good (HDL) cholesterol.
They also were more likely to be physically inactive, be a current smoker and have higher levels of obesity (BMI).  This association appeared to occur in only one direction--depression predicted later higher inflammatory markers, high inflammatory markers did not predict subsequent development of depression.

When potential key inflammatory confounding variables were controlled (BMI, smoking and inactivity), the association of depression and higher inflammatory biomarkers washed out.    The authors note that this finding suggests the inflammation linked to depression in heart disease may be amenable to increased efforts to "improve health behaviors".

It is unclear from this study how many subjects received pharmacotherapy or psychotherapy for a diagnosis of depression.  Primary treatment of depression may be necessary to engage and motivate those with depression and heart disease to improve their lifestyle choices and behaviors.

Photo of sunset in Santa Fe, New Mexico from the author's collection.

Duivis, H., de Jonge, P., Penninx, B., Na, B., Cohen, B., & Whooley, M. (2011). Depressive Symptoms, Health Behaviors, and Subsequent Inflammation in Patients With Coronary Heart Disease: Prospective Findings From the Heart and Soul Study American Journal of Psychiatry, 168 (9), 913-920 DOI: 10.1176/appi.ajp.2011.10081163

Improving Diagnostic Accuracy of Bipolar Disorder

A key clinical challenge in the mood disorders is to determine whether patients with depression actually have a diagnosis of bipolar disorder.  This can be quite difficult as patients may have limited insight while suffering a manic episode.  They may have impairments in memory during manic episodes that reduce their ability to provide an accurate psychiatric history.

The symptoms of mania are outlined in the Diagnostic and Statitistical Manual-Fourth Edition, Text Revision (DSM-IVTR) and include:

A. A distinct period of elevated, expansive or irritable mood lasting at least one week

B. Presence of three of the following symptoms or signs (four if irritable mood is assessed)

• inflated self esteem or grandiosity
• decreased need for sleep
• hypertalkative
• flight of ideas (moving quickly from one subject to another), racing thoughts
• distractibility
• increase in goal-directed activity or psychomotor agitation
• engagement in pleasurable activities with high risk for adverse out, i.e. gambling

C. Not accompanied by current symptoms of depression in which case a mixed episode is diagnosed

D. Significant impairment or psychotic symptoms or need for hospitalization

E.  Not better accounted by drug use, i.e amphetamines, a medical condition, or caused by a medical treatment for depression, i.e. antidepressants

Jules Angst and colleagues from the BRIDGE study group have recently published a study suggesting additional criteria may be helpful in diagnosing bipolar disorder in those with a history of depression.  Angst has previously proposed a bipolar specifier in depression populations that includes presence of a family history of bipolar disorder and an early-onset of illness with multiple mood episodes.

Using a international sample of over 5000 adults with ongoing major depression, Angst and his team closely examined a series of variables and determined the correlation with DSM-IV TR bipolar disorder diagnosis as well as the broader specifier criteria criteria.

The study found that a family history of mania or hypomania and multiple episodes of mood disorder did highly correlate with both DSM-IV criteria of mania.  Additionally, manic or hypomanic states during antidepressant therapy, presence of mixed mood disorder and comorbid substance abuse correlated with his bipolar specifier definition.

Using the limited DSM-IV TR mania/hypmanic criteria classifed 16% of the depressed sample as bipolar, while using the bipolar specifier increased this proportion to 47% of the sample.

The are significant clinical implications if this larger estimate of the percentage of individuals with depression meeting a bipolar variant is correct.  It would support greater use of mood stabilizers such as lithium, greater use of atypical antipsychotics such as aripiprazole and reduced use of the standard antidepressant class of drugs.  Antidepressants appear to have adverse effects on the long-term course of some individuals with the bipolar variant of mood disorder.

Dr. Gary Sachs of Harvard has also done work looking a similar expanded Bipolarity Index classification of mood disorder provided with this link.

Photo of Juno Beach sunrise using a pixelation filter from the author's collection.

Angst J, Azorin JM, Bowden CL, Perugi G, Vieta E, Gamma A, Young AH, & for the BRIDGE Study Group (2011). Prevalence and Characteristics of Undiagnosed Bipolar Disorders in Patients With a Major Depressive Episode: The BRIDGE Study. Archives of general psychiatry, 68 (8), 791-798 PMID: 21810644

Vilazodone: A Novel Antidepressant

Vilazodone was approved by the Food and Drug Administration in the U.S. earlier this year, but is just now becoming available in pharmacies for prescription use.  The drug is marketed in the U.S. under the trade name Viibyd.  It is novel in that it the only antidepressant that combines two mechanisms that can increase serotonin in the brain cortex: selective serotonin reuptake inhibition and partial agonism of the 5HT1A receptor.  There are multiple selective serotonin reuptake inhibitors, i.e. fluoxetine (Prozac), sertraline (Zoloft), and escitalopram (Lexapro).  

There are also compounds that have an agonistic effect on the 5HT1A receptor.  These include:
Antidepressants: trazodone, nefazodone
Antianxiety drugs: buspirone
Atypical antipsyhotics: aripiprazole, ziprasidone, clozapine, asenapine
Illicit drugs/compounds: MDMA (ecstasy), LSD, psylocybin, cannabidiol (cannabis)
Antimigraine compounds: ergotamine
Other compounds: yohimbine

The combination of SSRI and 5HT1A agonist effect may synergistically increase serotonergic transmission.  

Two published clinical trials on vilazodone are available on PubMed.  The table below summarizes some of the key findings from the two published trials.

The dose of vilazodone studied was 40 mg in both studies.  Because of the common occurrence of gastrointestinal side effects, doses are typically initiated at a smaller level and increased to 40 mg over the first week or so.  The pattern and prevalence of gastrointestinal side effects with vilazodone appears similar to levels seen in previous SSRI trials.  Although headache was commonly reported with vilazodone, the rate did not differ from the rate endorsed by placebo.  Dizziness, dry mouth, insomnia and abnormal dreaming were endorsed at a higher level with vilazodone but by less than 10% of the subjects.

Although vilazodone was statistically superior to placebo on almost all depression measures, it was not statistically superior in remission rates in the Kahn study.  This finding along with the relatively low absolute response rate of 27.3% in the vilazodone group is a little disappointing.

The response and remission rates found in these two studies were similar to SSRIs.  Head to head comparison with an SSRI would be informative to see if vilazdone has any effectiveness or adverse event superiority.  Sexual side effects are common with the SSRIs and the two randomized vilazodone studies reported no difference in sexual side effects between vilazodone and placebo.  Additionally, the Rickels study showed some evidence for anxiety symptom reduction.  Clinical trials examining the effectiveness of vilazodone for anxiety disorders will likely be soon completed.

Disclosure:  The author has no stock in the parent company of vilazodone (Forest Labs).  Additionally no honoraria or research grant support has been received related to this drug.  The author received no reimbursement for writing this post and the comments are entirely those of the author.

Information on the agonists for the 5HT1A receptor obtained from Wikipedia.

Chemical molecular structure of vilazodone from Creative Commons file at Wikepedia by author Meodipt.

Rickels K, Athanasiou M, Robinson DS, Gibertini M, Whalen H, & Reed CR (2009). Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial. The Journal of clinical psychiatry, 70 (3), 326-33 PMID: 19284933


Khan A, Cutler AJ, Kajdasz DK, Gallipoli S, Athanasiou M, Robinson DS, Whalen H, & Reed CR (2011). A randomized, double-blind, placebo-controlled, 8-week study of vilazodone, a serotonergic agent for the treatment of major depressive disorder. The Journal of clinical psychiatry, 72 (4), 441-7 PMID: 21527122