Expert: Ivan Goldberg, M.D. - 12/6/2010

Question
My 22 yo son had a major depression at 18 and 4 years later, many meds, many psychiatrist..and ETC he is still no better. He has stayed strong, no drink, no drugs, no sucidie attempts but says everyday is a living hell. I am afraid he will give up one day and take his life. Any ideas, my ex an I are heartbroken and lost for hope and help.
thank you

Answer
Hi Geri . . .

Chronic depression, especially bipolar depression, is accompanied by in increased risk of suicide. The best way to minimize the risk of suicide is by treating the depression, with both psychotherapy and medication, so that the depressive symptoms are not simply reduced, but eliminated. The aim of treatment should be remission not improvement.

Unless there is a critical physiological reason for not using it, lithium should be part of the long-term management. Lithium has been shown to lessen the likelihood of suicidal behaviors. This has not been shown for any other mood stabilizer. Below are a few abstracts of articles from medical journals supporting the use of lithium.

1. J Affect Disord. 2008 Apr;107(1-3):23-8. Epub 2007 Aug 16.

Divalproex, lithium and suicide among Medicaid patients with bipolar disorder.

Collins JC, McFarland BH.

Department of Psychiatry, CR-139, Oregon Health & Science University, Portland,
Oregon 97239, United States.

BACKGROUND: Suicide completion and attempted suicide are major concerns for
people with bipolar disorder. Studies in the private sector have suggested that
lithium treatment may be superior to divalproex therapy with regard to minimizing
suicidal behavior among individuals with bipolar disorder. However, few data are
available regarding Medicaid patients diagnosed with bipolar disorder. METHODS:
Subjects were 12,662 Oregon Medicaid patients diagnosed with bipolar disorder and
treated with medication between 1998 and 2003. Outcomes measures were completed
suicide and emergency department visits for suicide attempts (including non-fatal
poisoning). Cox proportional hazards models were used to adjust for demographics,
co-morbidity, and concurrent psychotropic medication use. RESULTS: Divalproex was
the most common mood stabilizer (used by 33% of subjects) followed by gabapentin
(32%), lithium (25%), and carbamazepine (3%). There were 11 suicide deaths and 79
attempts. Adjusted hazard ratios (versus lithium users) for suicide attempts were
2.7 for divalproex users (p<0.001), 1.6 for gabapentin users (not significant)
and 2.8 for carbamazepine users (not significant). For suicide deaths, the
adjusted hazard ratios were 1.5 for divalproex users (not significant), 2.6 for
gabapentin users (p<0.001), and not available for carbamazepine users.
LIMITATIONS: It should be noted that subjects were not assigned at random to
medication use, data on prior suicide attempts were not available, medication use
was measured by automated pharmacy records, and duration of mood stabilizer
utilization may have been brief. CONCLUSIONS: Lithium may have a protective
effect with regard to suicide attempts among Medicaid patients with bipolar
disorder. It remains unclear whether or not lithium protects these patients
against completed suicide.


PMID: 17707087 [PubMed - indexed for MEDLINE]


2. Psychiatr Prax. 2007 Sep;34 Suppl 3:S292-5.

[Pharmacological suicide prevention under special consideration of lithium salts]

[Article in German]

Müller-Oerlinghausen B.

Brain Center Berlin. bmoe@zedat.fu-berlin.de

OBJECTIVE: This minireview summarizes the existing evidence from large,
international observational studies and RCTs on the suicide preventive effects of
lithium as compared to other mood stabilizers and antidepressants. METHODS:
Unsystematic literature review. RESULTS: There is increasing and robust evidence
from a relatively large number of studies and metaanalyses that lithium long-term
treatment reduces the suicide risk and overall mortality in patients with all
kinds of depressive disorders (unipolar, bipolar, schizoaffective). Comparable
evidence does not exist with regard to other mood stabilizers including atypical
neuroleptics, or antidepressants. CONCLUSIONS: The existing evidence on the
suicide preventive effect of lithium should be integrated in therapeutic
guidelines and routine psychiatric care.


PMID: 17786886 [PubMed - indexed for MEDLINE]


3. Arch Gen Psychiatry. 2005 Aug;62(8):860-6.

Suicide risk in patients treated with lithium.

Kessing LV, Søndergård L, Kvist K, Andersen PK.

Department of Psychiatry, University Hospital of Copenhagen, Rigshospitalet,
Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. lars.kessing@rh.dk

CONTEXT: Prior observational studies suggest that treatment with lithium may be
associated with reduced risk of suicide in bipolar disorder. However, these
studies are biased toward patients with the most severe disorders, and the
relation to sex and age has seldom been investigated. OBJECTIVE: To investigate
whether treatment with lithium reduces the risk of suicide in a nationwide study.
DESIGN: An observational cohort study with linkage of registers of all prescribed
lithium and recorded suicides in Denmark during a period from January 1, 1995, to
December 31, 1999. SETTING: All patients treated with lithium in Denmark, ie,
within community psychiatry, private specialist practice settings, and general
practice. PARTICIPANTS: A total of 13 186 patients who purchased at least 1
prescription of lithium and 1.2 million subjects from the general population.
MAIN OUTCOME MEASURE: All suicides identified on the basis of death certificates
completed by doctors at the time of death. RESULTS: Patients who purchased
lithium had a higher rate of suicide than persons who did not purchase lithium.
Purchasing lithium at least twice was associated with a 0.44 reduced rate of
suicide (95% confidence interval, 0.28-0.70) compared with the rate when
purchasing lithium only once. Further, the rate of suicide decreased with the
number of prescriptions of lithium. There was no significant interaction between
continued lithium treatment and sex and age regarding the suicide rate.
CONCLUSION: In a nationwide study including all patients treated with lithium, it
was found that continued lithium treatment was associated with reduced suicide
risk regardless of sex and age.


PMID: 16061763 [PubMed - indexed for MEDLINE]


4. JAMA. 2003 Sep 17;290(11):1467-73.

Suicide risk in bipolar disorder during treatment with lithium and divalproex.

Goodwin FK, Fireman B, Simon GE, Hunkeler EM, Lee J, Revicki D.

Department of Psychiatry, George Washington University Medical Center,
Washington, DC 20037, USA. fgoodwin@mfa.gwu.edu

Comment in:
   JAMA. 2003 Sep 17;290(11):1517-9.
   JAMA. 2004 Feb 25;291(8):939; author reply 940.
   JAMA. 2004 Feb 25;291(8):939; author reply 940.

CONTEXT: Several studies have suggested that lithium treatment reduces risk of
suicide in bipolar disorder, but no research has examined suicide risk during
treatment with divalproex, the most commonly prescribed mood-stabilizing drug in
the United States. OBJECTIVE: To compare risk of suicide attempt and suicide
death during treatment with lithium with that during treatment with divalproex.
DESIGN AND SETTING: Retrospective cohort study conducted at 2 large integrated
health plans in California and Washington. PATIENTS: Population-based sample of
20 638 health plan members aged 14 years or older who had at least 1 outpatient
diagnosis of bipolar disorder and at least 1 filled prescription for lithium,
divalproex, or carbamazepine between January 1, 1994, and December 31, 2001.
Follow-up for each individual began with first qualifying prescription and ended
with death, disenrollment from the health plan, or end of the study period. MAIN
OUTCOME MEASURES: Suicide attempt, recorded as a hospital discharge diagnosis or
an emergency department diagnosis; suicide death, recorded on death certificate.
RESULTS: In both health plans, unadjusted rates were greater during treatment
with divalproex than during treatment with lithium for emergency department
suicide attempt (31.3 vs 10.8 per 1000 person-years; P<.001), suicide attempt
resulting in hospitalization (10.5 vs 4.2 per 1000 person-years; P<.001), and
suicide death (1.7 vs 0.7 per 1000 person-years; P =.04). After adjustment for
age, sex, health plan, year of diagnosis, comorbid medical and psychiatric
conditions, and concomitant use of other psychotropic drugs, risk of suicide
death was 2.7 times higher (95% confidence interval [CI], 1.1-6.3; P =.03) during
treatment with divalproex than during treatment with lithium. Corresponding
hazard ratios for nonfatal attempts were 1.7 (95% CI, 1.2-2.3; P =.002) for
attempts resulting in hospitalization and 1.8 (95% CI, 1.4-2.2; P<.001) for
attempts diagnosed in the emergency department. CONCLUSION: Among patients
treated for bipolar disorder, risk of suicide attempt and suicide death is lower
during treatment with lithium than during treatment with divalproex.


PMID: 13129986 [PubMed - indexed for MEDLINE]


5. J Clin Psychiatry. 2003;64 Suppl 5:44-52.

Lithium treatment and suicide risk in major affective disorders: update and new
findings.

Baldessarini RJ, Tondo L, Hennen J.

Department of Psychiatry and Neuroscience Program, Harvard Medical School,
Boston, MA, USA. rjb@mclean.org

BACKGROUND: Evidence that therapeutic benefits of psychiatric treatments include
reduction of suicide risk is remarkably limited and poorly studied. An exception
is growing evidence for such suicidal risk reduction with long-term lithium
maintenance. This report updates and extends analyses of lithium treatment and
suicides and attempts. METHOD: We pooled data from studies providing data on
suicidal acts, patients at risk, and average exposure times with or without
lithium maintenance therapy, and considered effects of lithium on selected
subgroups. RESULTS: Data from 34 reported studies involved 42 groups with lithium
maintenance averaging 3.36 years, and 25 groups without lithium followed for 5.88
years, representing 16,221 patients in a total experience of 64,233 person-years.
Risks for all suicidal acts/100 person-years averaged 3.10 without lithium versus
0.210 during treatment (93% difference) versus approximately 0.315 for the
general population. For attempts, corresponding rates were 4.65 versus 0.312 (93%
difference), and for completed suicides, 0.942 versus 0.174 (82% difference).
Subjects with bipolar versus various recurrent major affective disorders showed
similar benefits (95% vs. 91% sparing of all suicidal acts). Risk reductions for
unipolar depressive, bipolar II, and bipolar I cases ranked 100%, 82%, and 67%.
Suicide risk without lithium tended to increase from 1970 to 2002, with no loss
of effectiveness of lithium treatment. CONCLUSION: The findings indicate major
reductions of suicidal risks (attempts > suicides) with lithium maintenance
therapy in unipolar >/= bipolar II >/= bipolar I disorder, to overall levels
close to general population rates. These major benefits in syndromes mainly
involving depression encourage evaluation of other treatments aimed at reducing
mortality in the depressive and mixed phases of bipolar disorder and in unipolar
major depression.


PMID: 12720484 [PubMed - indexed for MEDLINE]

Best regards . . .

Ivan
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