I am going to list off all my disclaimers and biases up front in this post.
Our Western culture has a messianic focus on turning losers into winners. I reject outright this narrow dichotomy being used as a way to define the human condition.
I do not accept that negative emotional or mental states are “bad” and that positive emotional or mental states are “good”.
In particular, I anticipate that major depressive disorder (MDD), as a clinical and very serious condition, actually impacts less than 1% of our populations. 30% of those diagnosed with depression have severe cases which, in the US, adds to 1.5% of the entire population. 1
The World Health Organization lists the prevalence of major depressive disorder globally as 8.5%, or approximately 600 million people. The DSM-5 (Diagnostic and Statistical Manual for Mental Illness, version five) coming out this year will also pump those numbers up considerably because bereavement (losing a loved one) will now be included as a facet of major depressive disorder. I’ll discuss that in more depth later in this post.
Carl Glover: Flickr.com
My Biases
My biases have been shaped over many years and with much reading and research. I’ll share as much as I am able on my conclusions to help you determine whether you feel those biases are either valid or invalid as you attempt to assess your own health concerns with your health professionals.
The primary biases of mine that are going to be relevant here are: my assessments of antidepressants and their use as the primary go-to treatment for depression; my refusal to adopt a medical construct for most forms of depression found in humans and animals; and my first-hand observations that, while anecdotal, shape my opinions and likely lead me to develop a strong confirmation bias. Let’s start in:
Antidepressants
I am comfortable stating that all the anti-depressant drug families (SSRIs, SNRIs, MAOIs, trycyclics and the atypicals) are monstrously over-prescribed, in particular both SSRIs and SNRIs.
I am also comfortable adopting the data that conclude any benefits derived from taking any specific prescription from the families of antidepressant drugs are twice as likely to be due to placebo effect than any pharmacological action. 2,3,4,5,6
The side-effects of these drugs are much more severe, signficant and under-reported such that patients are unable to assess true risk/benefit costs to these prescriptions before they begin taking them.
Suicide Risk: Yes or No?
Many of you are aware there is tremendous controversy as to whether antidepressants actually increase suicide rates (usually by hanging) or not.
“Because of the low incidence of suicide, it is not possible to rule out either a threefold increase or a decrease in its occurrence among people treated with SSRIs. Large trials, randomising around 2 million individuals, would be required to detect an important effect on risk.” 7
I quote the above researcher and his team because it is a solid meta-analysis. They also uncovered in their review and assessments that self-harm does increase in a statistically important way with patients on antidepressants, although without the kinds of enormous longitudinal trials they suggest are needed, chance cannot be completely ruled out for that either.
Whenever insufficient data are available, I fall back on the precautionary principle.
“In most cases, European consumers and the associations which represent them must demonstrate the danger associated with a procedure or a product placed on the market… under the precautionary principle, the producer, manufacturer or importer may be required to prove the absence of danger.” 8
Given that there is a risk, based on Gunnell’s assessments, that you might be three times more likely to attempt suicide while taking an antidepressant, then I place the burden of proving that such a risk is not the case on the manufacturers of antidepressants. However, as these drugs are on the market already and it falls to the consumer to assess risk, all patients should be made fully aware that their risk of suicide may increase or decrease threefold if they begin taking antidepressants.
Antidepressants were “black boxed” by the FDA in 2004. The FDA required all manufacturers of antidpressants include a new black box label on the prescription packaging to indicate that the risk of suicidality in children and adolescents increases when they are taking these drugs.
Gagging the Scientists
Here in Canada we have developed quite the reputation of gagging our scientists. Scientists and researchers who work within either hospital or university settings are ostensibly considered independent arbiters, ensuring that the public is made aware of their research findings without any interference from either political interest or commercial organizations.
The tenure system within universities was originally implemented to remove the possibility of losing your job if you happened to publish research findings that were controversial, or embarrassed either political or commercial interested parties outside the university.
As the tenure system has eroded in almost all Western countries, and funding is now almost exclusively provided by interested commercial organizations, more scientists experience more harassment and pressure to bury research findings that do not support the funding body’s goals.
Two particularly high profile cases in Canada include: Dr. Nancy Olivieri and Dr. David Healy. And Dr. David Healy’s case is pertinent here because he had a job offer at the University of Toronto rescinded after he presented a lecture that was critical of clinical trials of psychiatric drugs, the practice of ghost writing in research publications, and he specifically spoke of the suicide risks associated with Prozac.
The maker of Prozac, Eli Lilly, provided half of the operating budget of the Mood and Disorder Clinic for the University of Toronto. You will find details entered into the public domain (by clicking on the link (his name) above ) regarding this case, as Healy enlisted the help of the Canadian Association of University Teachers to sue the University of Toronto on the grounds that the retraction of the job offer effectively compromised academic freedom. The case was settled out of court with Healy accepting a visiting professorship role at U of T.
“If Pharma made cars, the seat-belt warning signs would be removed, and the beeping noise if you moved without a seat-belt on would be silenced, as the start of a gradual process that would result in seat-belts being removed or made non-functional. The safety-bags would be removed or made ornamental. The car would be turbo-charged. The accelerator would be re-engineered so that the only options were travel at the upper end of the speed limit or faster.
The car would come with a Driver (Dr.). You could not get one without this option. The law would be adjusted so that in the case of any untoward event, legal liability falls on the Dr. rather than the manufacturer.” 9
Both Healy’s blog and his book Let Them Eat Prozac are worth reading. There are very few within the research and science communities these days who are both willing and able to risk their jobs and reputations in these ways, and that is why the gagging of scientists is a pernicious undercurrent that makes it even more difficult for patients to make informed decisions.
Side-Effects and Practitioner Response
“The strongest scientific evidence we have is not how well antidepressants work, but how badly they perform and how harmful they may be to certain individuals.” 10
Generally side-effects of taking trycyclics and MAOIs are more severe and that is why these antidepressants are often prescribed when the patient has initially failed to respond to SSRI or SNRI treatment.
The drop-out rates for patients who begin taking antidepressants sits at one-third, according to meta-analyses of clinical trials. 11 Very few trials include the reason for subjects leaving the trial, of those that do, both lack of efficacy and side effects are given as the most common reasons for dropping out. 12
There are no clinical data that suggest persevering with an antidepressant for up to six months that did not provide any relief for your symptoms within the first two weeks is at all valid. Yet this is a common recommendation you will receive from your prescribing physician when you relay that you are experiencing unpleasant side effects and not really noticing much relief in your overall depression.
There are however some reasonable initial data that suggest if a patient experiences improvement in their symtpoms within the first 14 days of taking the antidepressant they are far more likely to reach remission. More importantly, those who had no improvement within 14 days had no improvement at day 28 as well. 13
Side effects such as sexual dysfunction and akathisia (the feeling like you have had 20 cups of coffee or an inner jumpiness sensation) are often brushed aside by practitioners and they urge patients to persevere with the prescription as “it takes time”. However, these symptoms are debilitating for many patients and perseverance with the prescription rarely eases the side effects or the underlying depressive symptoms.
Cardiovascular side-effects of antidepressants are of significant concern for patients with co-occurring eating disorders and these risks are rarely imparted to them.
“…recent studies have demonstrated that the new SSRIs and antipsychotics also exert potent cardiovascular depressant effects in various mammalian and human cardiovascular preparations by inhibiting cardiac and vascular Na+, Ca2+ and K+ channels.” 14
There is also solid data to suggest that increasing dose is an ineffective way to generate symptom alleviation when an antidepressant is not providing any symptom alleviation within those first two weeks at initial dosing levels. 15,16,17
And finally, the recommendation that patients remain on antidepressants to prevent relapse, while having staunch expert panel support (American Psychiatric Association treatment guidelines, 2000), is not supported by a linchpin trial I will get into shortly. 18
Antidepressant Withdrawal or Discontinuation Syndrome
Before we look at that linchpin trial, I also want to address the fact that next to no patient is made aware, prior to starting an antidepressant drug treatment, that antidepressant withdrawal syndrome may actually render some incapable of ever tapering off of the prescription once they begin to take the drug.
46% of all patients coming off of antidepressants will experience symptoms associated with withdrawal from these drugs: dizziness, nausea, lethargy and headache. 19 The symptoms will occur for at least 6 weeks and there are no associations as yet with age, sex or diagnosis in identifying those likely to suffer discontinuation syndrome. 20,21,22
It is extremely difficult to find good data on prolonged discontinuation syndrome, but initial small trial data suggest perhaps 15% may have intractable, untreatable withdrawal or discontinuation symptoms even one year after cessation of an antidepressant. 23
Withdrawal from all classes of antidepressants should be done slowly and dose should be tapered down over many weeks. However, withdrawal symptoms seem to occur at the same rate (about 45%) whether tapering is done quickly or slowly. 24
Most severe symptoms include mania and/or hypomania as well as something nicknamed “brain zaps”. Brain zaps are best described as very sharp and painful electrical jolts that a patient feels within her head. These jolts are sufficient to wake the patient from sleep.
If we assume that the 15% rate of protracted discontinuation symptoms (beyond 12 weeks) will be borne out in future research, then 17 million people worldwide are dealing with unrelenting symptoms associated with antidepressant prescription cessation that can currently only be alleviated by putting the patient back on the antidepressant permanently.
And while human beings naturally discount future negative impacts when faced with possible immediate benefits, it is nonetheless important for you and your healthcare provider to discuss whether your depression is best treated with antidepressants at this particular juncture in your life, weighing up symptom severity and impacts on quality of life of course.
STAR*D Trial
Now we’ll take a look at the linchpin trial on the efficacy of antidepressants.
The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) was a randomized multi-site trial involving over 4000 subjects who were all outpatients with non-psychotic major depressive disorder. 25
Subjects were started on citalopram (Celexa), however 77.8% of those would not have met randomized controled trial requirements for inclusion in the trial. Those who would have met RCT guidelines were slightly more likely to reach remission (34.4% vs. 24.7%). 26
There were four phases to the trial where subjects who did not achieve remission in the first phase, were entered into subsequent phases to attempt to have the subject achieve remission from major depressive disorder.
The trial was attempting to mimic real-world experience and effectiveness of antidepressants for those diagnosed with major depressive disorder.
Critically, this trial also provided 12 months of follow-up data to determine whether remissions were maintainable or not as well.
Unlike a real-world scenario, subjects in the STAR*D trial actually received heightened follow-up to maximize adherence to treatment compared to what an average patient might receive in an outpatient community setting.
“Even with the extraordinary care of STAR*D, only about one fourth of patients achieved remission in step 1. The study dropout rate was slightly larger than the success rate. The success rate of step 2 was slightly less than that of step 1 and the dropout rate was larger. The success rates in step 3 (17.8%) and step 4 (10.1%) were even more modest with still larger dropout rates (44.8 and 60.1%, respectively).” 27
Cognitive therapy was an option for those who entered Phase II, but only 101 patients contributed any data (after randomization). The possible reasons for this therapy not being considered by the bulk of the subjects are presumed to be as follows:
- A biased self-selection towards pharmaceutical treatment (all patients were on citalopram in Phase I)
- Cognitive therapy costs were not covered for subjects in the STAR*D trial (which in fact mimics real-world options for patients)
- Subjects had to go to another site to receive cognitive therapy as well. 28
Of the 101 who underwent CT, they experienced equivalent remission rates to those receiving antidepressant treatment. While I suggest cognitive behavioural therapy (CBT) in support of reaching remission from an eating disorder, I think that the STAR*D trial certainly reflects many of the barriers that mimic real-world barriers for most patients pursuing this type of treatment for neurobiological conditions.
““In other words, if you’re trying to look at sustained benefit [for treatment of major depressive disorder], you’re only looking at 2.7%, which is a pretty jaw-dropping number,” added Dr. Pigott.” 29
Pigott and his colleagues conclude that, given the abysmal remission rates, it is perhaps not patients who are “treatment resistant” but rather the treatment that is largely inapplicable and ineffective for the patients. 30
And perhaps treatment, of any sort, is not required for the vast majority diagnosed with major depressive disorder in any case.
Major Depressive Disorder: The Definition
To qualify for diagnosis of MDD, you must have five of the following symptoms for two weeks or more, almost every day, and it has changed your level of functioning (summarized DSM-IV-tr):
- Depressed mood, or loss of interest (feels sad or empty) as identified by self-report or observation of others.
- Diminished interest or pleasure in activities most of the day nearly every day.
- Confirmed weight loss (when not dieting) or weight gain, or decrease/increase in appetite.
- Insomnia or hypersomnia (too little/too much sleep) nearly every day.
- Psychomotor agitation or retardation (fidgety or lethargic) observable by others
- Fatigue or loss of energy nearly every day
- Excessive feelings of worthlessness, inappropriate guilt (not just self-reproach about being sick)
- Diminished ability to think, concentrate, or indecisiveness either by self-report or observation of others.
- Recurring thoughts of death (not merely fear of dying). Suicide ideation (thinking about suicide without a specific plan), suicide attempt or specific plan for committing suicide.
The symptoms cannot meet the criteria for a mixed episode (meaning bi-polar cycles of mania and depression). The symtpoms are causing distress or impairment in social, occupational or other important areas of functioning. The symptoms are not due to the physiological effects of a substance (drug abuse, medications) or another general medical condition.
There was additionally the text associated with the exclusion of bereavement from MDD diagnosis unless the symptoms persisted beyond two months and were severely debilitating. That text will be removed from DSM-V indicating that you can receive an intstant diagnosis of MDD following the death of a loved one as well.
What is completely lacking in the exclusion criteria is whether the patient has a good reason to be depressed.
Benefits Of Depression
Isabella Blow, fashion icon and sometime muse to Alexander McQueen, killed herself at age 48. She was diagnosed with bipolar disorder in 2004 and underwent electroshock therapy which appeared to help her. However shortly afterwards she was diagnosed with ovarian cancer.
She attempted suicide in 2005 by jumping from the Hammersmith flyover, sustaining severe injuries. In 2006, she attempted suicide again with an overdose of sleeping pills, and in 2007 she ended her life in an agonizing and slow way by ingesting poison. 31
I include Isabella Blow here because she is a representative of a likely hereditary (two other family members had committed suicide), intractable and dangerous expression of a neurobiological condition and I want to make it clear that when I speak of the benefits of depression I do not include those with what would be identified as severe major depressive disorder (either uni or bi-polar depression).
As with eating disorders, MDD is a spectrum disorder. There are survival benefits for these neurobiological conditions on an evolutionary scale, but at times individuals can be predisposed to, and develop, a debilitating and unremitting case that could not possibly be viewed as having any benefits.
Occasionally I use the far more simplistic example of sickle-cell anemia to suggest that genetic traits can persist in our populations because there are benefits to some forms of expression of the genes.
An individual who inherits the sickle-cell trait from one parent has oblong shaped red blood cells. These are unappealing to the malarial trophozoites but pass comfortably through the patient's veins and arteries. 32 However, if an individual inherits the sicle-cell trait from both parents, she develops sickle-cell anemia. The blood cells are now shaped like tiny sickles and these do not pass comfortably through the blood stream.
Neurobiological conditions all have hereditary foundations, however it is not as simple as sickle-cell traits. The expression of a genotype linked to a particular neurobiological condition is heavily dependent upon environmental inputs because the brain is a social organ—it changes with social, cultural and environmental inputs.
We could essentially say that Isabella Blow experienced the equivalent of sickle-cell anemia, in a neurobiological sense. And for these individuals I wholeheartedly support any and all medical and psychological interventions that might possibly improve their quality of life in any way.
However, mercifully, those with extreme and severe depression are rare indeed.
For the vast majority who have a predisposition to depressive emotional and mental states, treatment may the last thing they need.
Concentration, Rumination, Focus and Depression
“Studies of rumination suggest that self-focused attention is maladaptive and perpetuates depression. Conversely, self-focused attention can be adaptive, facilitating self-knowledge and the development of the alternative functional interpretations of negative thoughts and feelings on which cognitive therapy of depression depends. Increasing evidence suggests there are distinct varieties of self-focus, each with distinct functional properties.” 33
There is a rather exciting and developing school of thought in the field of psychology that is turning the medicalization of neurobiological conditions on its head.
While the “sickle-cell anemia” presentation of neurobiological conditions is unerringly destructive, the vast majority are likely experiencing genotypic expressions of conditions that are highly adaptive and provide overall resilience for the individual and likely his or her children as well.
Those who inherit a tendency to ruminate or brood, also appear to inherit a tendency to develop a persistent depressive state. 34
Intriguingly, a behavior you would not assume to be at all linked to the onset of depression appears to be urgency. Urgency is the psychological term used to define acting without thinking, acting rashly, or acting impulsively.
In a study of 1,906 grade-school children, researchers tested whether fifth-grade urgency predicted sixth-grade impulsive behavior, and whether it could predict sixth-grade depressive states as well. Fifth-grade urgency predicted sixth-grade depression. 35
Smith and colleagues theorize that urgency may have transdiagnostic value that can lead to those who develop a cycle of rash actions and high-risk behaviors and others who develop a state of ill-advised inaction.
But is such inaction ill-advised? Perhaps not. If a fifth grader responds to the consequences of acting rashly by withdrawing, ruminating and brooding, then we might be falling victim to our cultural bias that action-oriented individuals are mentally healthier than inaction-oriented individuals. We presume inaction is maladaptive.
There are likely both adaptive and maladaptive forms of rumination. In fact, task-focused thinking after a failure facilitates performance improvement. 36,37
When a concrete form of self-focused symptom-based rumination is applied with depressed patients, their social problem solving skills improve. 38 What is concrete self-focused symptom-based rumination? Basically, looking at specifics of a circumstance that may have triggered withdrawal rather than creating universal truths on which you brood.
As an example, imagine an urgency-prone fifth-grader impulsively agrees to leave the school grounds at lunch with friends, something that is not allowed in that school. She and her friends are all inevitably caught; visit the principal’s office; have lunchtime playground cleanup duties assigned; and have to take a note home to their parents that must be signed to confirm the parents are aware their child broke the rules.
Should the child be prone to rumination, then with just a bit of gentle direction from her parents, she can develop concrete self-focused symptom-based rumination in response to her breaking the rules.
She could easily slip into broad and vague self-focused concepts: “I am a bad person”, “I am stupid and silly”, or “Everyone hates me” in response to the distress and embarrassment she may feel at having publicly shunned social cohesion and acceptability (following the rules). With some guidance she can develop concrete self-focused rumination that may look more like: “I did not think through the consequences of breaking the rules at the time”, “I remember that Kevin told us not to go, so I could get advice from him in future”, or “I am not a bad person, I made a mistake”
Reinforcing adaptive rumination applies for depression-prone adults as well. If you catch yourself using broad, vague self-loathing statements when you revisit past perceived failures or transgressions, then you know you are practicing maladaptive rumination.
“The analytical rumination hypothesis proposes that depression is an evolved response to complex problems, whose function is to minimize disruption and sustain analysis of those problems by (a) giving the triggering problem prioritized access to processing resources, (b) reducing the desire to engage in distracting activities (anhedonia), and (c) producing psychomotor changes that reduce exposure to distracting stimuli.” 39
Translated, it appears that shutting the world out, not wanting to interact, and concentrating on a problem at hand is the upside of a genetic predisposition towards a depressed state as it allows for an enhanced ability to solve complex problems.
Depression Has Value
Those with depression are actually more skilled at solving social dilemmas. 40
“Sometimes people are reluctant to disclose the reason for their depression because it is embarrassing or sensitive, they find it painful, they believe they must soldier on and ignore them, or they have difficulty putting their complex internal struggles into words. But depression is nature’s way of telling you that you’ve got complex social problems that the mind is intent on solving.” (emphasis mine). 41
Depression has a strong equivalent expression in all animals when they are ill or wounded. Robert Sapolsky discusses this in further detail in his book: Why Zebras Don’t Get Ulcers. There are biological advantages to withdrawing from social interaction and reducing exposure to external stimuli in terms of hastening and facilitating healing. If you have ever tended a sick cat or dog, you know that they often appear aloof, down, reclusive and unwilling to interact.
Not surprisingly, the monstrously complex 5HT-receptor family and subfamily genotypes (implicated in everything from migraines to anxiety to eating disorders) are also involved in the expression of depression. 42
“Studies of depression in rats show that the 5HT1A receptor is involved in supplying neurons with the fuel they need to fire, as well as preventing them from breaking down. These important processes allow depressive rumination to continue uninterrupted with minimal neuronal damage, which may explain why the 5HT1A receptor is so evolutionarily important.” 43
Unlike other animals, we also have a tool available to us to develop adaptive rumination behaviors so that we might maximize depressive states as a tool for healing, rather than presuming it to be a disease state necessitating medical intervention to be “healed”.
Write It Down
There are numerous studies that suggest developing adaptive ruminative skills, resolving complex social dilemmas and easing depressive symptoms are best achieved by expressive writing, or journaling. 44,45,46,47,48,49
Depression is not improved with volunteering efforts for all but those over age 65. 50,51,52,53
And yes, exercise has very little impact on depression despite common understanding:
“There were 28 trials (1101 participants) that included a comparison of exercise with either waiting list or placebo; overall, we found exercise seemed to improve the symptoms of depression. However, when only the high-quality trials were included, the effect on depression was small. More research is needed to confirm these findings.” (emphasis mine) 54
Anecdotal Observation
I have a family stuffed full of both depressives and those with anxiety. My own observations suggest that depression does not occur in the absence of a pre-existing anxiety disorder.
It is likely that the hyper-vigilance associated with anxiety leads to secondary depression precisely because the cognitive load of vigilance is exhausting and requires periods of withdrawal in order to both recharge and find sustainable approaches that support healing.
I am currently dealing with the grief of losing one of my beloved cats. I am insulted and reject outright that the process should be identified as a disease state.
I am a staunch proponent of Pascal Boyer’s theories that identify religion as a by-product of brain function. His incredibly dense book, Religion Explained, identifies that the process of accepting the death of a loved one involves a strange disconnection between memory, agency and understanding misfortune, among other intuitions.
Critical Incident Stress Debriefing (CISD), an intervention that is ostensibly meant to reduce the chance of post-traumatic stress disorder continues to be widely applied across Western countries immediately after any crisis (school shootings being a tragic and most common application for CISD in the US). However in experimentation, CISD actually heightens the chance of developing PTSD. 55
The process of integrating either the loss of a loved one, or the experience of some traumatic event, requires space and time for the integration to be successful. I am going to go into much more detail on this topic in a subsequent blog post, but if you would like a head start, then look out Redirect by Timothy D. Wilson.
Depression, like grief, is a process of examination, reinterpreting experiences, trimming and sculpting memories through revisiting them. And always there is an opportunity to learn.
I have both family members and friends who take antidepressants. I have family members and friends who take anxiolytics. I have many family members and friends who have been prescribed antidepressants for anxiety.
Some experience placebo benefit, many more have experienced severe side-effects both while taking antidepressants and while attempting to wean off of them. Of those who have been on anxiolytics (primarily benzodiazepines) long term, none have developed tolerance to date.
I do not take antidepressants or anxiolytics. I have both a propensity for anxiety and depression, presumably due to hereditary factors given its prevalence in my family.
I have found tremendous benefit in developing adaptive rumination, although in all honesty I had no idea that was what I was doing and I have happened upon that approach rather organically as a result of lots of reading over the years. I journal.
Distress tolerance is an emotional muscle to exercise and develop in life. I no longer view my predisposition to an anxious or depressive state as inherently bad or wrong. Both provide me with an ability to greatly improve my overall distress tolerance and that inherently assures increased resilience in simply living life.
So at the end of 5000+ words, what do you do if you are depressed while attempting recovery?
Use expressive writing to journal your way through the complex dilemmas that the recovery process is throwing at you. Don’t forget there is the Recovery Journal available to purchase that is specifically designed for recovery from an eating disorder.
There is likely a fairly significant component of grief and loss through the recovery process, primarily associated with how you have created and reinforced identity and self-worth.
However, grief is not a disease state, nor should it be identified as major depressive disorder either.
And finally, although I can personally say that pet guardianship has generated tremendous overall emotional health benefits for me, in fact the clinical jury is out on who will, or will not, achieve mental and physical health benefits from having a pet in their lives.
Still, sometimes anecdotal information is enough.
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2. Kirsch, Irving, and Guy Sapirstein. "Listening to Prozac but hearing placebo: A meta-analysis of antidepressant medication." Prevention & Treatment 1, no. 2 (1998): 2a.
3 Kirsch, Irving, Thomas J. Moore, Alan Scoboria, and Sarah S. Nicholls. "The emperor's new drugs: an analysis of antidepressant medication data submitted to the US Food and Drug Administration." Prevention & Treatment 5, no. 1 (2002): 23a.
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8. Summaries of EU Legislation
9. DHealy, davidhealy.org, March 30, 2012
10. http://www.mcmanweb.com/antidepressants.html
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12. ibid.
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15. Kirsch, Irving, Thomas J. Moore, Alan Scoboria, and Sarah S. Nicholls. "The emperor's new drugs: an analysis of antidepressant medication data submitted to the US Food and Drug Administration." Prevention & Treatment 5, no. 1 (2002): 23a.
16. Kirsch, Irving, Alan Scoboria, and Thomas J. Moore. "Antidepressants and placebos: secrets, revelations, and unanswered questions." (2002): 33r.
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18. Pigott, H. Edmund, Allan M. Leventhal, Gregory S. Alter, and John J. Boren. "Efficacy and effectiveness of antidepressants: current status of research." Psychotherapy and psychosomatics 79, no. 5 (2010): 267-279.
19. Haddad, Peter M., and Ian M. Anderson. "Recognising and managing antidepressant discontinuation symptoms." Advances in Psychiatric treatment 13, no. 6 (2007): 447-457.
20. Haddad, Peter M., and Angelika Wieck. "Antipsychotic-induced hyperprolactinaemia." Drugs 64, no. 20 (2004): 2291-2314.
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22. Warner, Christopher H., William Bobo, Carolynn Warner, Sara Reid, and James Rachal. "Antidepressant discontinuation syndrome." American family physician 74, no. 3 (2006).
23. Fava, Giovanni A., Manuela Bernardi, Elena Tomba, and Chiara Rafanelli. "Effects of gradual discontinuation of selective serotonin reuptake inhibitors in panic disorder with agoraphobia." International Journal of Neuropsychopharmacology 10, no. 6 (2007): 835-838.
24. Phelps, James. "Tapering antidepressants: is 3 months slow enough?." Medical hypotheses 77, no. 6 (2011): 1006-1008.
25. Rush, A. John, Maurizio Fava, Stephen R. Wisniewski, Philip W. Lavori, Madhukar H. Trivedi, Harold A. Sackeim, Michael E. Thase et al. "Sequenced treatment alternatives to relieve depression (STAR* D): rationale and design." Controlled clinical trials 25, no. 1 (2004): 119-142.
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27. Pigott, H. Edmund, Allan M. Leventhal, Gregory S. Alter, and John J. Boren. "Efficacy and effectiveness of antidepressants: current status of research." Psychotherapy and psychosomatics 79, no. 5 (2010): 267-279.
28. Thase, Michael E., Edward S. Friedman, Melanie M. Biggs, Stephen R. Wisniewski, Madhukar H. Trivedi, James F. Luther, Maurizio Fava et al. "Cognitive therapy versus medication in augmentation and switch strategies as second-step treatments: a STAR* D report." American Journal of Psychiatry (2007).
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