Both for the antidepressants and anti psychotics switch tables are made. Clicking on the appropriate switch continues to an explanation and switch schedule with links to Medscape, Pubmed, PubChem, Wikipedia and several other websites for more information. The benzodiazepines calculator can help you switch from one to another benzodiazepine.
Depressed patients often do not respond to there first antidepressant or have to quit the antidepressant due to side effects. Switching to another antidepressant is often a solution. Nevertheless switching from one to the other depressant can be difficult. How do you switch, which taper scheme and which built up scheme do you use. How is this influenced by the cytochrome P450 system?
Also shown is a way to stimulate rodent brains with light using light sensitive proteins in rodents, called optogenetics. It makes a nice model for activity in the brain during depression. It’s an example of how new tools and research are shedding light on brain structures that may play an integral role in treating depression.
Depression is also accompanied by cognitive distortions negative self beliefs. This is effectively treated with cognitive behavioral therapy. In this video it’s explained how brain scans can illuminate effects of CBT on depression
Very informative video, nicely made and luckily made availble.
50 to 60 % of patients with a depressive disorder fail to respond to their first antidepressant. These rates increase in clinical practice setting to 65 to 85%. Estimates of treatment resistant depression (TRD) prevalence varies greatly depending on treatment setting. The lowest TRD prevalence is in primary care and progressively higher rates occur in outpatient psychiatric settings, inpatients settings and academic tertiairy setting.
What is Treatment-Resistant Depression?
An inadequate response to an adequate course of treatment in a patient meeting criteria for major depressive disorder. Treatment is usually antidepresssants. Depression is not bipolar depression. This diagnoses needs a different approach. An adequate course is a course of an adequate dosage of the antidepressant for at least 6 weeks.
What can they do about Treatment-Resistant Depression?
Besides the 9 steps for treatment resistant depression described in an earlier post on this blog systematic treatment algorithms do decrease inappropriate variance and can be used to increase the use of appropriate treatment strategies to enhance patient outcome. Rigorous treatment management can enhance outcome. An treatment algorithm is a standardized stepwise drug treatment regimen. Protocols are used based on sequential application of a variety of single therapeutic steps. We discussed such a treatment algorithm in a previous post about the 9 Steps for Treatment Resistant Depression. In this algorithm, 129 (87%) of 149 patients achieved response. Complete remission was achieved by 89 of 149 (60%) patients. A German observational 2-year pilot study to evaluate effectiveness, feasibility, and acceptance among algorithm users also showed a big improvement in response. The total response rate was 72%. The acceptance rate of an algorithm by algorithm naive physicians was moderate to say the least: patient inclusion rate of only 48%.
These algorithms are mainly used in a clinical setting. In contrast to the US a considerable portion of depressed patients, especially with severe depression and/or treatment resistant depression are admitted for on average 40 days in The Netherlands, specially the 1500mg cannabinoid drops that are getting very popular when treating this disease .
The German group recently published the results of a randomized, controlled, single-center algorithm study to evaluate treatment efficacy and treatment process compared with treatment as usual (TAU).
Their conclusion was:
Algorithm-guided treatment produces better outcomes and less frequent medication changes than TAU. A systematic, stepwise, measurement-based approach to the treatment of depressed inpatients is warranted.
Their algorithm consisted of 10 steps. First patients were withdrawn from medication and diagnosed. Than sleep deprivation was used, if non or not enough response an antidepressant was started on standard dose for 2 weeks (amitriptyline, venlafaxine, paroxetine or nortriptyline), the next step was a high dose of the antidepressant followed by lithium addition, followed by lithium monotherapy in case of non response, combined with a monoamine oxydase inhibitor (tranylcypromine), high dose MAO-inhibitor in combination with lithium and if that didn’t work finally ECT. in the TAU group physicians were free to apply whatever treatment they thought appropriate.
They included 148 patients, 74 in each group. Of the 74 patients randomized to the algorithm group, 40 (54%) achieved remission compared with only 29 (39%) in TAU, in the algorithm group patients had a 2 fold probability of remission in a given time interval (see picture for survival analysis).
The strength of this trial was the randomized comparison with a treatment as usual group. The superiority of algorithm guided treatment has been demonstrated in previous studies. The only drawback in study is the relatively high drop out rate due to adverse events and protocol violations due to physician’s non compliance stressing the importance of adherence to the ideas about algorithms. This kind of stepwise treatment protocols depend on support from all members of the team. Ideally the algorithm is designed by the treatment team as a whole.
Bauer, M., Pfennig, A., Linden, M., Smolka, M., Neu, P., & Adli, M. (2009). Efficacy of an Algorithm-Guided Treatment Compared With Treatment as Usual Journal of Clinical Psychopharmacology, 29 (4), 327-333 DOI: 10.1097/JCP.0b013e3181ac4839
Most airlines don’t allow their pilots flying when on antidepressants. In Australia they have a better attitude to this problem, because to my opinion it is better to have a pilot on antidepressants than a depressed pilot.
This conclusion was substantiated by results research: A study presented at a conference of the World Psychiatric Association in Melbourne on Friday found no statistical difference between medicated and non-medicated pilots in terms of their safety record. But importantly, there was a tendency for more accidents in the period prior to pilots going on to anti-depressants, but not once they were on them.
This blogger pilot is at home, he is not allowed to fly.
I have done a great deal in my life. I have much to offer, yet I still do not see myself as worthwhile unless I am at the controls of an airplane.
We discussed a prior publication in the Archives of General Psychiatry about the decline of antidepressants use after the FDA black box warning. In a more recent study published in the same journal this prior study was criticized because it had some serious limitations. The study used prevalent use instead of incidence use. This means, used all cases instead of the new cases that started using antidepressants and they included all use instead of the use for depression. Antidepressant indications range from major depression to smoking cessation and weight loss, with varied suicidality risk. The warning for heightened suicidality risk was targeted at depressed patients.
This new study used new antidepressant users from the targeted group (children, adolescents, younger adults 18-24 years) and a comparison group of nontargeted adults over a long period from 1997 to 2007 in a large cohort.
Diagnosing decreases persist. Substitute care did not compensate in pediatric and young adult groups, and spillover to adults continued, suggesting that unintended effects are nontransitory, substantial, and diffuse in a large national population.
In all age groups, 5-18, 18-24 and 25-89, depression diagnosis rates were significantly lower than history predicted based. More specific 44% lower for pediatric, 37% lower for young adults, 29% for adults.
The decline in SSRI prescriptions was 10-15%. Not only did SSRI prescriptions decrease in the targeted populations from 5-18 and 18-24 but it also had an unintended effect. The same decline persists in the adult cohort, which was never a target of the advisory or warnings. Luckily no increase in prescriptions of atypical antipsychotics or anxiolytics for depression was found. Psychotherapy increased significantly for adult, though not pediatric, cases.
In the recent numbers of British Journal of General Practice articles were published about depression in General Practice. In The Netherlands about 80% of patients with a depression visit the GP. In The Netherlands it’s estimated that in 2003 about 856.000 people in a year suffer from depression. That’s 6.3% on a population of 16 million people in a year. Of these 80% of depressed visiting the GP 66% receives a treatment of which 50% solely in primary care.
A recent meta-analysis of randomized studies examining psychological treatments in primary care depressed patients was published in the British Journal of General Practice. The review included 15 studies with variable quality. Psychological treatment of depression was found to be effective in primary care, especially when General Practitioners refer patients with depression for treatment. When screening tools were used to identify cases of depression psychological treatment didn’t work better than no treatment.
Psychological treatment of depression in primary care is not less effective than in other settings. The overall number needed to treat (NNT) was 5.75, this means that for every 5.75 patients randomized to psychological treatment instead of the control treatment, one additional remitted patient was observed. This is comparable to a meta-analysis of antidepressant treatment in primary care that found an NNT for selective serotonin reuptake inhibitors of around 6.0.
Between one third and one-half of patients stop taking the antidepressant within 3 months, and less than half continue to take their antidepressant medication for a full 6 months. It has been found that overall (that is, all prescriptions and all therapeutic groups), between 7% and 20%of patients fail to redeem their prescription at the pharmacy.
But what happens with first time prescriptions of an antidepressant. The general practitioner (GP) and patient have decided to start treatment with an antidepressant. One in four patients who receive a prescription for an antidepressant for the first time do not take the antidepressant or do not use it longer than for 2 weeks. These patients consulted their GP for non-specific indication such as sleeping problems, fatigue, relationship problems. Non-Western immigrants and patients older than 60 years were more likely to decline treatment.
This compares to drop-out rates for psychological therapies of about 30% and poses a particular challenge for health care professionals.
Also it is very important for GP’s to monitor the severity of depression. Before starting treatment with an antidepressant the severity of the depression needs assessment. Most physicians though confuse severity assessment with diagnoses. These severity scales such as the Beck Depression inventory and the Zung Scale are only applicable when a depression has been diagnosed preferably by a trained clinician such as the GP. If a severity scale is used by a GP does this lead to the proper referrals to specialist services for depression? From a recent published study in the UK GP’s diagnosis of depression is associated with greater severity most of these patients were treated with antidepressants (80%) and around 20% were referred to specialists services.
The efficacy of depression treatment in primary care is far from excellent and comparable to other settings. Moreover, the GP has an important function in indicating and the treatment of depression in primary care. Screening doesn’t add more value. The use of severity scale confirms that GP’s diagnosis of depression is associated with greater severity and leads to antidepressant treatment for moderate to severe depression or referral to specialist services. However, depression severity scales shouldn’t be used as diagnostic scales
The GP has advantages above other settings. They usually have a trusting relationship with their patients, they know a lot of their background, that’s why I am an supporter of good primary care, makes health care a lot more efficacious and cheaper. Be aware of those specialists.
What do you think?
Boardman, J., & Walters, P. (2009). Managing depression in primary care: it’s not only what you do it’s the way that you do it British Journal of General Practice, 59 (559), 76-78 DOI: 10.3399/bjgp09X395049 van Geffen, E., Gardarsdottir, H., van Hulten, R., van Dijk, L., Egberts, A., & Heerdink, E. (2009). Initiation of antidepressant therapy: do patients follow the GP’s prescription? British Journal of General Practice, 59 (559), 81-87 DOI: 10.3399/bjgp09X395067 Cuijpers, P., van Straten, A., van Schaik, A., & Andersson, G. (2009). Psychological treatment of depression in primary care: a meta-analysis British Journal of General Practice, 59 (559), 51-60 DOI: 10.3399/bjgp09X395139 Kendrick, T., Dowrick, C., McBride, A., Howe, A., Clarke, P., Maisey, S., Moore, M., & Smith, P. (2009). Management of depression in UK general practice in relation to scores on depression severity questionnaires: analysis of medical record data BMJ, 338 (mar19 1) DOI: 10.1136/bmj.b750
In a recent study published in the Journal of the American College of Cardiology, depressive symptoms were associated with an increased risk of fatal coronary Heart Disease (CHD) in relatively healthy women with no prior coronary disease. Depressive symptoms especially antidepressant use were also associated with sudden cardiac death (SCD).
One of the main advantages of this study was the prospective design and the inclusion of a large group (n=63,469) of women without coronary disease, stroke, or malignancy. They were followed for cardiovascular events and depression on follow-up between 1992 and 2004. Most prior studies were retrospective observational studies with depressed patients who often exhibit coronary risk factors, in most studies not all risk factors could be accounted or adjusted for in the statistical analysis. Many studies fail to record body mass index, serum lipids, physical inactivity, all of which might contribute to coronary heart disease.
The weak point of this study is the lack of proper diagnosis of the depression. As most often a diagnosis was based on an insufficient scale, this time the depression was defined on a 5-point mental health index score and antidepressant use. The questionnaire was administered every 2 years.
This way it is unclear whether it was real depression or those with severe cardiovascular disease who had a bad prognosis. Patients with severe somatic illness often present wit “depressive symptoms” which is only to be attributed to their worse somatic condition based on their medical condition.
A recent meta-analysis reported that when depression was identified from scores, it was less strongly associated with CHD than when diagnosed by experts
Because diagnosis with golden standard such as psychiatric experts with standardized clinical interview was not performed some nurses participating in this study might have had mild depression, depressive symptoms or have been misdiagnosed. Moreover, overlap between anxiety disorders, depressive disorder and somatoform disorders or comorbidity of these disorders can be confounding the results when solely a scale is used instead of expert diagnosis.
Another surprising result was that the use of antidepressant medications was associated with an elevated risk of sudden cardiac arrest (SCA), and that this explained most of the CHD events associated with major depression. Most subjects (61%) used selective serotonin reuptake inhibitors. Previous research is unclear whether SSRIS are related to SCA. Maybe it was just the “depression” alone? More studies are necesaary to solve this issue whether the “depression” or the antidepressants causes SCA. The prescription of antidepressants, if done properly, far outweighs the risk of SCA.
Why is this important?
Moreover, if antidepressant use merely indicates severe depression, these results could suggest that depression should actually be treated more aggressively. Thus, at the present time, the absence of proof that antidepressants might cause cardiac events is more relevant than conclusive proof that this effect is absent. Nevertheless, these findings are sufficiently sobering to warrant heightened clinical surveillance and to initiate studies to definitively address this relationship.
Narayan, S., & Stein, M. (2009). Do Depression or Antidepressants Increase Cardiovascular Mortality?The Absence of Proof Might Be More Important Than the Proof of Absence⁎ Journal of the American College of Cardiology, 53 (11), 959-961 DOI: 10.1016/j.jacc.2008.12.009
Whang, W., Kubzansky, L., Kawachi, I., Rexrode, K., Kroenke, C., Glynn, R., Garan, H., & Albert, C. (2009). Depression and Risk of Sudden Cardiac Death and Coronary Heart Disease in WomenResults From the Nurses’ Health Study Journal of the American College of Cardiology, 53 (11), 950-958 DOI: 10.1016/j.jacc.2008.10.060
Psychiatrists in the United Kingdom and The United States of America and probably also in The Netherlands hardly use scales to measure outcome when treating depressed patient. In mental health clinic or outpatient units the evaluation is typically based on unstructured interactions leading to unquantified judgment of progress. Imagine a primary physician or internist not measuring temperature, white blood cell count etc when someone has pneumonia. Or a GP not measuring blood pressure after a patient has started with anti hypertensive medication. In mental health care standardized, quantifiable outcome measures exist but hardly used.
You don’t have to do a weekly severity scale such as the Hamilton Depression Rating scale as in research but at least use it when starting an antidepressant and when deciding on outcome before you switch or augment. One of the few good results of STAR*D was the advocacy of the importance of using scales to measure outcome: “measurement based care”.
In the UK 11.2% of 340 psychiatrists routinely used outcome measures when treating depression and anxiety disorders. In the US less than 10% almost always used scales to monitor outcome, more than half of the 314 psychiatrists indicated that they never or rarely used scales to monitor outcome.
They believed that using scales would not be clinically helpful
That the scales would take too much time to use
That they were not trained in their use
They preferred to assess outcome “clinically”
The groups of those using scales routinely and those not using scales were comparable on all characteristics, no differences in gender, age, years of practice, or practice setting.
Most of the reasons for not using scales to measure outcome for depressed patients are probably based on the use of the Hamilton Rating Scale for Depression or the Montgomery-Asberg Rating Scale rather than thinking of self-report scales such as the Beck Depression Inventory or the Zung Depression Ratings scale. These hardly cost time or training. They are valid and reliable measures of severity of depression.
In our residency program we start our training with an Introduction week. In this week they receive education on important topics to start doing their work especially for their work when on call. The training with the Hamilton Depression Rating Scale for Depression is the least valued part of the whole week.
Do you use outcome measures when treating depressed patients and do you educate your residents and train them for using these rating scales, let me know in the comments.
Zimmerman, Mark, & McGlincey, Joseph B. (2008). Why Don’t Psychiatrists Use Scales to Measure Outcome When Treating Depressed Patients? Journal of Clinical Psychiatry, 69, 1916-1919 DOI: 19192467
Why is maintenance antidepressant therapy important?
Of patients with a depressive disorder 50% will have further episodes
The recurrence rate of depression is 80 to 90% after 3 episodes
Poor adherence to treatment of chronic conditions such as depressive disorder is a large problem
Nonadherence rates in recurrent depressed patients range from 39.7% to 52.7% with a mean of 46,5% over 2 years
Suboptimal dosing and duration of antidepressants increases the risk of relapse and recurrence.
Clinicians are only 50% accurate in their identification of potentially nonadherent patients.
Patch Testing Patch Test Services is соmmоnlу uѕеd to іdеntіfу саuѕеѕ of аllеrgіс contact dermatitis. Whеn performed рrореrlу, it саn bе interpreted аѕ ѕсіеntіfіс рrооf оf allergic соntасt dеrmаtіtіѕ. Thе раtсh test dоеѕ nоt nесеѕѕаrіlу duplicate сlіnісаl exposure іn whісh ѕwеаtіng, mасеrаtіоn, multiple applications оf a рrоduсt mау рlау rоlеѕ іn producing a ѕkіn reaction іn rеаl lіfе еxроѕurе of thе ѕkіn to a соntасt аllеrgеn.. Patch tеѕtіng however іѕ a better mеthоd оf fіndіng оut a cause оf an оffеndіng аllеrgіс contactant, thеn dоіng clinical trіаl. If аn allergen can bе соrrеlаtеd wіth a known exposure, роѕіtіvе patch tеѕt оr іmрrоvеmеnt bу avoidance оf ѕubѕtаnсеѕ соntаіnіng the аllеrgіс contactant іndеntіfіеd bу patch tеѕtіng then thе роѕіtіvе раtсh tеѕt іѕ validated. Unfortunately, mаnу dеrmаtоlоgіѕtѕ аѕ wеll аѕ allergists dо nеglесt tо perform patch tеѕtѕ tо іdеntіfу the causes оf аllеrgіс соntасt dermatitis. At Thе Asthma Cеntеr, wе hаvе hаd decades оf еxреrіеnсе dоіng patch tеѕtѕ and іdеntіfуіng significant аllеrgіс соntасt rеасtіоnѕ.
When a super-sensitive person comes in contact with the substance that causes the allergy (called an allergen), the immune system overreacts and releases a large amount of a chemical called histamine. Large amounts of histamine cause tissue swelling (inflammation) and tightening (constriction) of muscles and other tissues, including those in the breathing passages. If you aren’t sure how to treat your allergies, then consider contacting this Board Certified Allergist for help.
What are the potential risk factors for nonadherence in patients with recurrent depressive disorder? This question was recently researched and published in the Journal of Clinical Psychiatry.
The researchers assessed nonadherence with the Medication Adherence Questionnaire. Nonadherence on this scale indicates that patients missed 20% or more of the doses of their antidepressant medication. They followed 91 patients with at least 2 major depressive episodes in the last 5 years and were in remission. Follow up duration was 2 years.
In a multivariate analysis with backward elimination they found a higher level of personality pathology and higher education at baseline predictive for for nonadherence during a follow up of 2 years. These two factors explained 15% of the variance in nonadherence. All other variables such as axis 1 comorbidity, number of previous episodes, severity of residual symptoms, severity and duration of last episode, and medication did not increase the risk of nonadherence. There was no independent variable predicting nonadherence.
Limitations of this study Besides the small sample which could have limited the power of the study resulting in a lack of identifying possible factors influencing nonadherence this study did not include other confounding factors for adherence in the patient doctor relationship such as the therapeutic alliance, patients attitudes towards the illness and the medication.
Ten Doesschate MC, Bockting CL, Koeter MW, Schene AH (2009). Predictors of nonadherence to continuation and maintenance antidepressant medication in patients with remitted recurrent depression. Journal of Clinical Psychiatry DOI: 19192463