DSM IV criteria for Seasonal Affective Disorder (SAD).
Any depressive disorder, be it recurrent depressive episode, major depressive episodes in bipolar I disorder, bipolar II disorder can have a seasonal pattern in which case the specification seasonal pattern can be applied if the following criteria apply.
a. There has been a regular temporal relationship between the onset of major depressive episodes and a particular time of year (e.g. regular appearance of the major depressive episode in autumn or winter)
b. Full remissions (or a change from depression to mania or hypomania) also occur at a characteristic time of year (e.g. depression disappears in the spring).
c. In the last 2 years, two major depressive episodes have occurred that demonstrate the temporal season relationship defined in criteria a and b, and no non-seasonal major depressive episode has occurred during the same period.
d. Seasonal major depressive episodes (as described above) substantially outnumber the non-seasonal major depressive episodes that may have occurred over the individual’s lifetime.
Note: Do not include cases in which there is an obvious effect of season-related psychosocial stressors (e.g. regularly being unemployed each winter)
Unlike classically depressed patients, most SAD patients develop ‘atypical’ symptoms of increased fatigue, increased sleep duration and increased appetite and weight. Not only do SAD patients crave carbohydrates, but also they actually report eating more carbohydrate-rich foods in the winter.
Especially these atypical symptoms and the disappearance of symptoms after the winter makes it hard to diagnose this variant of depression.
How is SAD treated with light therapy?
An excellent recent post about SAD explains treatment of SAD with light therapy: More Than Coping: Seasonal Affective Disorder
Bright white fluorescent light has been shown to reverse the winter depressive symptoms of SAD. Early studies used expensive “full-spectrum” bulbs, but these are not especially advantageous. Bulbs with color temperatures between 3000 and 6500 degrees Kelvin all have been shown to be effective. The lower color temperatures produce “softer” white light with less visual glare, while the higher color temperatures produce a “colder” skylight hue. The lamps are encased in a box with a diffusing lens, which also filters out ultraviolet radiation. The box sits on a tabletop, preferably on a stand that raises it to eye level and above. Such an arrangement further reduces glare sensations at high intensity, and preferentially illuminates the lower half of the retina, which is rich in photoreceptors that are thought to mediate the antidepressant response. Studies show between 50% and 80% of users showing essentially complete remission of symptoms, although the treatment needs to continue throughout the difficult season in order to maintain this benefit.
A lot is written and has been written about SAD in blog posts, treatment, causes, symptoms, you can find links to 8 Blogs in this article on this blog: 8 articles about Seasonal Affective Disorder
A mutual help group is defined as a group of people sharing a similar problem, who meet regularly to exchange information and to give and receive psychological support, like Alcohol Anonymous. Traditionally, groups meet face to face, but internetbased groups have expanded rapidly in recent years.
In a recently published review of 12 studies meeting strict inclusion criteria mutual help groups provide limited but promising evidence that mutual help groups benefit people with three types of problems: chronic mental illness, depression/anxiety, and bereavement.
Seven of the 12 studies reported some positive changes in mental health for group members. The strongest findings come from two randomized studies showing that the outcomes of mutual help groups were equivalent to those of established, more costly, professionally provided psychological interventions. Five of the 12 studies found no differences in mental health outcomes between mutual help group members and non-members; no studies showed any evidence of negative effects. There was no indication that mutual help groups were beneficial for certain types of problems but not others.
Strenghts of mutual help groups:
they utilize support from people who have gone through similar difficulties and participants therefore can easily empathize with each other
This may compensate for deficiencies in people’s natural support networks
group members possess ‘‘experiential knowledge’’, in contrast to the professional knowledge of service providers
Mutual Self Help groups and Depression
One excellent trial compared group behavioral therapy (CBT) and mutual help groups for depression, both professionally and non-professionally (peer) led. Self-report measures as well as ratings by an independent clinician were used to assess the change between before and after treatment. Participants improved on all measures, the outcomes of the mutual help groups being equivalent to those of the CBT groups, and peer leaders were as effective as professional therapists. Peer led groups are far more inexpensive than professional led groups.
In this group the only Internet based study of internet support groups was included. They used a longitudinal design to assess depressive symptoms over time. One-third of members showed a resolution of depressive symptoms with more frequent users more likely to improve (after adjusting for a number of other variables). Control group was lacking.
The third study included in the depression group studied self-help groups for adults hospitalized for unipolar or bipolar depression. Alas due to methodological flaws no conclusion can be drawn from this trial.
So for depression, mutual self help groups might be of benefit.
Evidence for efficacy of mutual self help groups is still in it’s infancy, what do you think?
The studies varied in terms of design quality and reporting of results. More high-quality outcome research is needed to evaluate the effectiveness of mutual help groups across the spectrum of mental health problems
Nancy Pistrang, Chris Barker, Keith Humphreys (2008). Mutual Help Groups for Mental Health Problems: A Review of Effectiveness Studies American Journal of Community Psychology, 42 (1-2), 110-121 DOI: 10.1007/s10464-008-9181-0
Major depression is a very heterogeneous diagnosis. Subtypes of depression such as melancholic, psychotic or atypical depression may differ not only in etiology and clinical picture, but also in clinical response to medical treatments. Do we need another subtype of depression, what do you think, let me know?
The last decades the working mechanisms of antidepressants haven’t changed very much, hence the name “me too drugs”. Moreover, current antidepressants are based on serendipitous discoveries rather than on bench-to-bedside, targeted drug discovery although clinically efficient antidepressant drugs do exist, the situation is in many cases far from ideal. Existing antidepressants have many shortcomings:
Low remission and/or high treatment-resistance rates
Slow onset of action
Side effects and drug–drug interactions
Wouldn’t it be nice if we had neurological, biological, and genetic data in future DSM classifications of Major Depression?
The current diagnostic criteria in the DSM classification systems represent clusters of symptoms and characteristics of clinical courses that do not necessarily describe homogeneous disorders and may rather reflect common final pathways of different pathological processes.
Arguments that stress plays an important role in the development of depression
Increasing evidences report gene environment effect in Major Depression, with stress often representing the key environmental trigger of MD onset in vulnerable individuals
Hypothalamo–pituitary–adrenocortical (HPA)-axis dysregulation due to chronic stress is confirmed to be an important parameter for treatment outcome in MD but it is neither a necessary nor a sufficient determinant for acute treatment response
Stress exposure conceivably plays a causal role in the etiology of MD and depression-like disorders. Neurotransmitters and neuropeptides, as well as conceptually novel immune and inflammatory mediators, are likely intermediate links between stress exposure, depressive symptoms, and MD
Animal models involving a chronic (i.e., continuous exposure to a threatening stimulus for a significant amount of time, usually weeks) or intermittent (i.e., daily short exposure to a threat for subsequent days) exposure to negative stressful events can be considered the most effective in modeling MD-associated behavioral and physiological disturbances. Also animal models in which the threatening stimulus is social in nature or models in which exposure to stressful stimuli occurs in the early postnatal or juvenile age are effective models for MD behavior in animals
Recently identification of genes overexpressed or downregulated in selected brain regions after chronic stress exposure are linked to major depression.
Stress Induced Depression is an entity developed by Swedish researchers.
A dramatic increase in the number of workers on longterm sick leave was observed between the years 1997 and 2003 (Statistics Sweden, 2004 ). Studies of consecutive cases with psychiatric diagnoses culled from the databases of two large Swedish insurance companies showed that about 80% of patients met DSM-IV criteria for MD
Characteristics of Stress Induced Depression:
The depression episodes were mild to moderate, and accompanied by significant working memory impairment.
It tended to have a prolonged course, and that the patients often remained in a state of exhaustion after the depressive symptoms had remitted. the remaining clinical picture was one of deep mental and physical fatigue, disturbed and non-restorative sleep, irritability, perceptual hypersensitivity, emotional liability, and pronounced cognitive disturbances (mainly memory and concentration problems).
The majority was clearly induced by psychosocial stress, either at the workplace or often in combination with stress factors in the family.
In contrast to other kind of depression the HPA-axis hypo-reactivity was found in STRID patients.
Dr Shock stayed out of the discussions about the STAR*D trials. The choice of treatments was absolutely not evidence based and the results could never by generalized to Europe or The Netherlands for that matter. A recent publication in Evidence Based Mental Health Care summarizes the difficulties of the STAR*D trials. If you need more information about this trial please visit the website: Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study
Difficulties with STAR*D
There was no placebo arm in level one of the trial. Primary care physicians offer support, explanation and time (‘‘wait and see’’) as important interventions in the management of low mood. This makes generalisability difficult for patients in primary care. In this trial about a third of patients were recruited from primary care and they have been offered the option of a wait and see or a placebo option. Moreover, I am an advocate for placebo controlled trials. You can read in this post for the reasons why: 7 Reasons for placebo controlled trials in depression.
To consent to inclusion in the trial participants had to find prescription of an antidepressant acceptable. This excludes those who would rather have psychotherapy as treatment option and probably explains why so few people chose to be randomised to a psychotherapy option in level two of the trial.
The choice of strategies appears hard to justify. Why choose buproprion and buspirone as initial augmentation strategies when there appears better evidence for augmentation with lithium? For other and better options as well as a better treatment algorithm read: 9 steps for treatment resistant depression
The lead investigators had significant relationships with the makers of the drugs used in the study.
Because of the diverse range of healthcare providers, the relative lack of primary care and the difficulty accessing care by people without insurance it is hard to generalise the results into non-US health settings.
The STAR*D trial may be the 300 lb gorilla of clinical trials but disappointingly it only sheds a little light on how to manage depression in clinical practice.
S. Hatcher (2008). The STAR*D trial: the 300 lb gorilla is in the room, but does it block all the light? Evidence-Based Mental Health, 11 (4), 97-99 DOI: 10.1136/ebmh.11.4.97
ScienceDaily (2008-12-03) — A new universal test to predict the risk of someone succumbing to major depression has been developed. The online tool, predictD, could eventually be used by family doctors and local clinics to identify those at risk of depression for whom prevention might be most useful.
The risk algorithm, developed by a team led by UCL Professors Michael King and Irwin Nazareth, was tested in 6,000 people visiting their family doctor in six countries in Europe (UK, Spain, Portugal, the Netherlands, Slovenia and Estonia). Its accuracy was also tested in nearly 3,000 GP attendees in a further country, Chile, in South America. The study, published in the Archives of General Psychiatry, followed-up the participants at six and 12 months. The team modelled their approach on risk indices for heart disease, which provide a percentage risk estimate over a given time period. The algorithm was as accurate at predicting future episodes of depression as similar instruments developed in Europe to predict future risk of heart problems.
Tried it myself, not your average magazine test. The makers must have studied and worked hard to make this test.
Michael King et al. Development and validation of an international risk prediction algorithm for episodes of major depression in general practice attendees. Archives of General Psychiatry, December 2008
There are considerable data to indicate that psychotic depression is not just a severe form of depression but a distinct form of depression. Mostly in terms of clinical symptoms, course, biology, treatment response and outcomes. However, not every difference is indisputable, there are inconsistencies among studies and these differences might not be strong enough to be used in diagnosis.
Differences in clinical symptoms 1. Unusual thought content, increased feelings of guilt and psychomotor disturbances such as agitation and retardation are the most robust differences compared to non psychotic depression for clinical symptoms.
Clinical Course 2. Early onset psychotic depression has been associated with a likely bipolar course.
Cognitive symptoms 3. The greatest cognitive impairments of psychotic depressed patients compared to nonpsychotic major depression were: verbal memory, executive functioning and psychomotor speed. An issue that remains is the medication use of psychotic depressed patients. Usually they are on more different drugs than the nonpsychotic depressed, especially antipsychotic which can influence the test scores.
Biological features 4. Psychotic depressed patients have higher rates of nonsuppression on the dexamethason suppresion test (64%) compared to nonpsychotic depressed patients (41%). The sensitivity and specificity are not high enough to use these tests routinely for diagnosis. Treatment response 5. ECT is very effective in the acute phase of the treatment of psychotic depressed patients. The data are unclear regarding the duration of this effect.
Issues involved with the distinction between the two types of depression:
1. What is called psychotic depression, hallucinations and delusions, and what kind of delusions, only mood congruent delusions? In Europe the presence of mood congruent delusions and hallucinations justifies the diagnosis psychotic depression. Should we look at dimensions of psychosis instead of a binary division?
2. In the DSM IV psychotic depression is linked to severity of the depression. The relationship between severity and psychotic features is not that strong. This implies a scale for severity and a separate classification for psychotic features.
3. The authors of the article promote a separate dimension for psychotic features with the loss of the distinction between mood congruent and mood incongruent delusions. A development not encouraged by Dr Shock.
4. Additionally more research is needed for the distinction between psychotic depression and schizoaffective disorder.
J. Keller, A. F. Schatzberg, M. Maj (2007). Current Issues in the Classification of Psychotic Major Depression Schizophrenia Bulletin, 33 (4), 877-885 DOI: 10.1093/schbul/sbm065
Methods for preventing the onset of new cases of depression are manifold. The most researched prevention methods are:
Cognitive Behavioral Therapy, the number of sessions can vary from 6-15 sessions. It can be given in a group or individual treatment.
Problem Solving. In short: Problem solving treatment has three main steps: patients’ symptoms are linked with their problems, problems are defined and clarified, and an attempt is made to solve the problems in a structured way. See also BMJ. It is usually done by primary physicians and nurses.
Psychoeducation emphasizes instruction not therapy and promotes relaxation, positive thinking, pleasant activities, and social skills. It can be done in a group or with individuals, the number of sessions can vary between 4-12.
Interpersonal therapy is a time-limited psychotherapy that focuses on the interpersonal context and on building interpersonal skills. IPT is based on the belief that interpersonal factors may contribute heavily to psychological problems. It is commonly distinguished from other forms of therapy in its emphasis on the interpersonal rather than the intrapsychic. Individual and/or group sessions varying from 6-15.
Social support is the physical and emotional comfort given to us by our family, friends, co-workers and others. In this form of treatment these forms of support are clarified and expanded or improved.
Any combination of these treatments
Prevention has been examined in a considerable number of intervention studies, but only a small proportion of these have focused on possibilities for actually preventing the onset of new cases of mental disorders. In a recent meta-analysis 19 studies could be included.
The number needed to treat to prevent one case of depressive disorder was 22. This means that 22 individuals have to be treated with a prevention treatment before 1 won’t have an onset of a depressive disorder.
There are three types of prevention:
Universal prevention, such as school programs and mass media campaigns, aimed at the general population or segments of the general population, regardless of whether they have a higher-than-average risk of developing a disorder
Selective prevention, aimed at individuals in high-risk groups who have not yet developed a mental disorder such as post partum women, stroke patients.
Indicated prevention, aimed at individuals who have some symptoms of a mental disorder but do not meet diagnostic criteria.
In this systematic review
Two of the 21 contrast groups we included in our meta-analysis examined universal prevention, 11 examined selective prevention, and eight examined indicated prevention. Fifteen interventions were cognitive-behavioral therapy (CBT), three were interpersonal psychotherapy,
and the remaining were other types of intervention (one-session debriefing; problem-solving; and
mutual support).
Not the type of prevention but prevention based on interpersonal psychotherapy may be more effective than prevention based on cognitive-behavioral therapy. Target population such as post partum women or adolescents did not influence the outcome of a prevention strategy.
The authors state in their article:
………the numbers needed to treat seem to be rather high (22 in the overall analysis). On the other hand, there are no clear guidelines for what is a high number needed to treat and what is not. For example, the regular use of aspirin to reduce the risk of heart attack has become common practice, and the number needed to treat has been found to be 130. The number needed to treat associated with the use of cyclosporine in the prevention of organ rejection has been found to be 6.3 and is considered a medical breakthrough of considerable practical importance.
What do you think is treating 22 individuals with a prevention program to prevent the onset of depression in one of them worth the time and money? Selective- and indicated prevention have lower numbers of needed to treat respectively 16 and 17.
Limitations of this study:
Small number of studies (19)
Quality of studies not all optimal
Limited follow-up, max 2 years
Pim Cuijpers, Ph.D., Annemieke van Straten, Ph.D., Filip Smit, Ph.D., Cathrine Mihalopoulos,, B.B.Sc.(Hons), Aartjan Beekman, M.D., Ph.D. (2008). Preventing the Onset of Depressive Disorders: A Meta-
Analytic Review of Psychological Interventions American Journal of Psychiatry, 165, 1272-1280 DOI: 18765483
Somewhere along the way we have lost our friendship and our love, and our lust for one another. My depression has really been hard on him. He seems to think I don’t know that. He avoids me by drinking and working. Myself, I feel like I am giving up on the relationship. Using the little energy I have to create and stimulate the growth of new friendships.
Compared to the marital interactions of nondepressed couples, the marital interactions of couples with a depressed partner are characterized by a higher frequency of negative communication behaviors (e.g., blame, withdrawal, verbal aggression) and a lower frequency of positive communication behaviors (e.g., self-disclosure, problem-solving behaviors, smiling, eye contact).
It is mostly unclear whether the problems could be due to depression, marital distress, or the interaction of the two factors. This question is important since uncertainty of interpretation could have negative clinical implications, as certain patterns of communication may be erroneously attributed to depression when they are actually related to marital distress.
Group of studies show that when marital distress levels are corrected for by statistical procedures, depressed and nondepressed couples continue to differ on communication behaviors, but the differences do not remain as strong
In studies comparing maritally distressed couples with a depressed partner and maritally distressed couples without a depressed partner, it appeared that couples who were experiencing both depression and marital distress engaged in more frequent depressogenic communication of self, personal well-being, and their future.
Studies comparing marital interactions in maritally distressed couples with a depressed partner to two comparison groups: nondepressed medical patients and nondepressed community comparison subjects it was found that the depressed and medical patients did not differ significantly from each other in terms of frequency of smiling, eye contact, and pleasant facial expressions. Moreover, both groups rated their marriages as less satisfactory than those of the nondepressed community sample. Problematic interpersonal behavior in both depressed and medical patients suggests that the behaviors that differentiated the couples in these groups from the couples in the community sample may be nonspecific behavioral markers of interaction where at least one partner is experiencing a negative life circumstance. In another study results showed that couples with a depressed husband could be reliably distinguished from couples with an alcoholic husband in terms of interactional sequencing. For example, compared to couples with an alcoholic husband, the marital interactions of couples with depressed husbands were characterized by less interdependency and less negative reciprocity. It remains to be seen if marital distress is specific for depression.
There is evidence indicating that women are more emotionally expressive and report higher levels of both positive and negative emotions and that they are more likely to display symptoms of depression and to seek help for mild levels of depression. Data suggest that women may have a greater interpersonal orientation toward, and responsibility for, the marital relationship. It is possible that men inhibit expression of depressive symptoms during social interactions. Four studies comparing the marital interaction between couples with a depressed wife or husband showed conflicting results. Some couldn’t find an influence of gender, some studies suggest that depressed females’ marital behaviors are
more impacted by their depression than are males. The numerous methodological differences in the studies may be contributing to these discrepant findings.
Conclusion
Marital distress is not specific for depression, the influence of gender on the marital distress is unknown. What is already known is that depressed women are significantly more likely to generate stressful interpersonal events, which both perpetuate depressed mood and set the stage for depressive relapse. Depression has interpersonal causes, is interpersonally mediated, and that interpersonal factors are linked to depression relapse. This should be taken into account when treating patients of both gender with depression.
What to do about it
The ones closest to the Depressed are often on “the front lines” of the depression battlefield, and they are sometimes unarmed with the necessary tools to cope. Compassion fatigue, a term used to describe those caregivers who have been unknowingly drained by another’s illness or care-needs, is often the result. It can test even the most secure of relationships.
U REHMAN, J GOLLAN, A MORTIMER (2008). The marital context of depression: Research, limitations, and new directions☆ Clinical Psychology Review, 28 (2), 179-198 DOI: 10.1016/j.cpr.2007.04.007
The findings of a recent study with a small sample size (n=22) suggests a possible benefit of maintenance treatment with sertraline over placebo. After an acute treatment phase of 12 weeks responders were followed during the continuation phase of 6 months. The patients who maintained response were randomized to either placebo or continued on sertraline.
None of the 9 subjects in the placebo group maintained response (no recurrence) during the 52-week randomization phase. In contrast, 5 of 13 subjects (38%) in the sertraline group remained well.
A lot of controversy has been raised around the use of antidepressants for adolescents suffering from depression. It was suggested that antidepressants increase the risk of suicide in adolescents as can be read in:“On the Antidepressant Suicide Link”. Conflicting results were published on the combination of cognitive behavioral therapy and antidepressants for depression in adolescents. You can read about a post describing beneficial effects and a post without this beneficial effect of the combination.
Fear of decreasing use of antidepressants for depression in adolescents causing increased suicides could not be demonstrated in the United States nor in The Netherlands.
This maintenance study however suggest that maintenance treatment may be beneficial to youth with major depressive disorder if they have responded and stayed well during follow-up (6 months). This is comparable to the maintenance treatment in adults. In adults continued treatment with antidepressants after acute response is critical in preventing recurrence in patients with major depression.
Limitations
Small sample size, Survival analyses found no significant differences between the groups. The acute phase was an open label trial. Lack of the inclusion of a specific suicide instrument
Amy Cheung, Vivek Kusumakar, Stan Kutcher, Elyse Dubo, Jane Garland, Margaret Weiss, Alex Kiss, Anthony Levitt (2008). Maintenance Study for Adolescent Depression Journal of Child and Adolescent Psychopharmacology, 18 (4), 389-394 DOI: 10.1089/cap.2008.0001
Gorman, J M (2006). Gender Differences in Depression and Response to
Psychotropic Medication Gender Medicine, 3 (2) DOI: 16860269
Gender differences in response to treatment
Several articles have explored the topic of gender differences in terms of response to antidepressants. In a 12-week multicenter, double-blind, randomized, parallel-group comparative trial pre-menopausal females showed higher response rates when taking sertraline, a selective serotonin reuptake inhibitor (SSRI), while men show higher response rates when taking imipramine, a tricyclic antidepressant (TCA), and post-menopausal females show similar response rates for both antidepressants (Kornstein et al., 2000).
It was concluded that women might respond better to SSRIs than to TCAs and that there is indeed a difference in response rate by menopausal status (Kornstein et al., 2000).
The results of most previous studies are comparable to this trial (Martenyi et al., 2001)(Raskin, 1974)(Davidson and Pelton, 1986)(Grigoriadis et al., 2003)(Thase et al., 2005)(Khan et al., 2005)(Berlanga and Flores-Ramos, 2006).
In a recent study with a large sample of real world patients from primary and psychiatric specialty care centers women were more likely to reach remission and response with citalopram than men (Young et al., 2008).
On the other hand, complementary studies have failed to find different response rates to antidepressants between men and women. Quitkin et al., performed a retrospective analysis on depressed outpatients (the majority with atypical depression) and concluded that the statistical significant difference in response rates to TCAs and monoamine oxidase inhibitors (MAOIs) based on gender and menopausal status was not clinically relevant (Quitkin et al., 2002).
Similarly, other studies concluded that there is no difference in antidepressant treatment response based on gender (Scheibe et al., 2003)(Hildebrandt et al., 2003)(Wohlfarth et al., 2004)(Thiels et al., 2005) or on menopausal status (Cassano et al., 2005).
Overall the conclusions regarding the influence of gender and menopausal status on antidepressant treatment response in depressed patients are inconsistent
References
Berlanga, C. & Flores-Ramos, M. (2006) Different gender response to serotonergic and noradrenergic antidepressants. A comparative study of the efficacy of citalopram and reboxetine. J Affect Disord, 95, 119-23.
Cassano, P., Soares, C. N., Cusin, C., Mascarini, A., Cohen, L. S. & Fava, M. (2005) Antidepressant response and well-being in pre-, peri- and postmenopausal women with major depressive disorder treated with fluoxetine. Psychother Psychosom, 74, 362-5.
Davidson, J. & Pelton, S. (1986) Forms of atypical depression and their response to antidepressant drugs. Psychiatry Res, 17, 87-95.
Grigoriadis, S., Kennedy, S. H. & Bagby, R. M. (2003) A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol, 23, 405-7.
Hildebrandt, M. G., Steyerberg, E. W., Stage, K. B., Passchier, J., Kragh-Soerensen, P. & Danish University Antidepressant Group. (2003) Are gender differences important for the clinical effects of antidepressants? Am J Psychiatry, 160, 1643-50.
Khan, A., Brodhead, A. E., Schwartz, K. A., Kolts, R. L. & Brown, W. A. (2005) Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol, 25, 318-24.
Kornstein, S. G. (1997) Gender differences in depression: implications for treatment. J Clin Psychiatry, 58 Suppl 15, 12-8.
Kornstein, S. G., Schatzberg, A. F., Thase, M. E., Yonkers, K. A., Mccullough, J. P., Keitner, G. I., Gelenberg, A. J., Davis, S. M., Harrison, W. M. & Keller, M. B. (2000) Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry, 157, 1445-52.
Martenyi, F., Dossenbach, M., Mraz, K. & Metcalfe, S. (2001) Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Eur Neuropsychopharmacol, 11, 227-32.
Quitkin, F. M., Stewart, J. W., Mcgrath, P. J., Taylor, B. P., Tisminetzky, M. S., Petkova, E., Chen, Y., Ma, G. & Klein, D. F. (2002) Are there differences between women’s and men’s antidepressant responses? Am J Psychiatry, 159, 1848-54.
Rasgon, N. L., Dunkin, J., Fairbanks, L., Altshuler, L. L., Troung, C., Elman, S., Wroolie, T. E., Brunhuber, M. V. & Rapkin, A. (2007) Estrogen and response to sertraline in postmenopausal women with major depressive disorder: a pilot study. J Psychiatr Res, 41, 338-43.
Raskin, A. (1974) Age-sex differences in response to antidepressant drugs. J Nerv Ment Dis, 159, 120-30.
Scheibe, S., Preuschhof, C., Cristi, C. & Bagby, R. M. (2003) Are there gender differences in major depression and its response to antidepressants? J Affect Disord, 75, 223-35.
Thase, M. E., Entsuah, R., Cantillon, M. & Kornstein, S. G. (2005) Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt), 14, 609-16.
Thiels, C., Linden, M., Grieger, F. & Leonard, J. (2005) Gender differences in routine treatment of depressed outpatients with the selective serotonin reuptake inhibitor sertraline. Int Clin Psychopharmacol, 20, 1-7.
Wohlfarth, T., Storosum, J. G., Elferink, A. J., Van Zwieten, B. J., Fouwels, A. & Van Den Brink, W. (2004) Response to tricyclic antidepressants: independent of gender? Am J Psychiatry, 161, 370-2.
Young, E. A., Kornstein, S. G., Marcus, S. M., Harvey, A. T., Warden, D., Wisniewski, S. R., Balasubramani, G. K., Fava, M., Trivedi, M. K. & Rush, J.A. (2008) Sex differences in response to citalopram: A STAR*D report
Continuing research is needed to determine how gender influences the risk, clinical presentation, and response to treatment of depression. Exploration of sex differences in animals and humans should aid in efforts to treat depression as an organic disorder rather than a psychological maladaptation.